ProFi Achievements
Publications
2019 |
Baxter, P N W; Ouahabi, Al A; Karmazin, L; Varnek, A; Strub, J M; Cianferani, S An Investigation into the Stephens-Castro Synthesis of Dehydrotriaryl[12]annulenes: Factors Influencing the Cyclotrimerization Article de journal European Journal of Organic Chemistry, 40 , p. 6783-6795, 2019, (2019-02). @article{652, title = {An Investigation into the Stephens-Castro Synthesis of Dehydrotriaryl[12]annulenes: Factors Influencing the Cyclotrimerization}, author = {P N W Baxter and A Al Ouahabi and L Karmazin and A Varnek and J M Strub and S Cianferani}, doi = {10.1002/ejoc.201901053}, year = {2019}, date = {2019-10-18}, journal = {European Journal of Organic Chemistry}, volume = {40}, pages = {6783-6795}, note = {2019-02}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Barre, A; Pichereaux, C; Velazquez, E; Maudouit, A; Simplicien, M; Garnier, L; Bienvenu, F; Bienvenu, J; Burlet-Schiltz, O; Auriol, C; Benoist, H; Rougé, P Insights into the Allergenic Potential of the Edible Yellow Mealworm (Ŧenebrio molitor) Article de journal Foods, 8 (10), 2019. @article{pmid31635354, title = {Insights into the Allergenic Potential of the Edible Yellow Mealworm (Ŧenebrio molitor)}, author = {A Barre and C Pichereaux and E Velazquez and A Maudouit and M Simplicien and L Garnier and F Bienvenu and J Bienvenu and O Burlet-Schiltz and C Auriol and H Benoist and P Rougé}, doi = {10.3390/foods8100515}, year = {2019}, date = {2019-10-18}, journal = {Foods}, volume = {8}, number = {10}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Voisinne, G; Kersse, K; Chaoui, K; Lu, L; Chaix, J; Zhang, L; Menoita, Goncalves M; Girard, L; Ounoughene, Y; Wang, H; Burlet-Schiltz, O; Luche, H; Fiore, F; Malissen, M; de Peredo, Gonzalez A; Liang, Y; Roncagalli, R; Malissen, B Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics Article de journal Nat. Immunol., 20 (11), p. 1530–1541, 2019. @article{pmid31591574, title = {Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics}, author = {G Voisinne and K Kersse and K Chaoui and L Lu and J Chaix and L Zhang and M Goncalves Menoita and L Girard and Y Ounoughene and H Wang and O Burlet-Schiltz and H Luche and F Fiore and M Malissen and A Gonzalez de Peredo and Y Liang and R Roncagalli and B Malissen}, doi = {10.1038/s41590-019-0489-8}, year = {2019}, date = {2019-10-07}, journal = {Nat. Immunol.}, volume = {20}, number = {11}, pages = {1530--1541}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Ayala-Nunez, NV.; Follain, G; Delalande, F; Hirschler, A; Partiot, E; Hale, GL.; Bollweg, BC.; Roels, J; Chazal, M; Bakoa, F; Carocci, M; Bourdoulous, S; Faklaris, O; Zaki, SR.; Eckly, A; Uring-Lambert, B; Doussau, F; Cianferani, S; Carapito, C; Jacobs, FMJ.; Jouvenet, N; Goetz, JG.; Gaudin, R Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells Article de journal Nat Commun. 2019 Sep 27;10(1):4430., 2019. @article{651, title = {Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells}, author = {NV. Ayala-Nunez and G Follain and F Delalande and A Hirschler and E Partiot and GL. Hale and BC. Bollweg and J Roels and M Chazal and F Bakoa and M Carocci and S Bourdoulous and O Faklaris and SR. Zaki and A Eckly and B Uring-Lambert and F Doussau and S Cianferani and C Carapito and FMJ. Jacobs and N Jouvenet and JG. Goetz and R Gaudin}, doi = {10.1038/s41467-019-12408-x}, year = {2019}, date = {2019-09-27}, journal = {Nat Commun. 2019 Sep 27;10(1):4430.}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
S, Hessmann Erb Rabuka Huguet Josephs Beck Drake PM Cianférani Hernandez-Alba Houel S S D R J A S O A Case Study to Identify the Drug Conjugation Site of a Site-Specific Antibody-Drug-Conjugate Using Middle-Down Mass Spectrometry Article de journal J Am Soc Mass Spectrom., 30 (11), p. 2419-2429., 2019. @article{649, title = {A Case Study to Identify the Drug Conjugation Site of a Site-Specific Antibody-Drug-Conjugate Using Middle-Down Mass Spectrometry}, author = {Hessmann Erb Rabuka Huguet Josephs Beck Drake PM Cianférani S S D R J A S Hernandez-Alba O Houel S}, doi = {10.1007/s13361-019-02296-2}, year = {2019}, date = {2019-09-19}, journal = {J Am Soc Mass Spectrom.}, volume = {30}, number = {11}, pages = {2419-2429.}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Schneider, F; Dureau, A -F; Hellé, S; Betscha, C; Senger, B; Cremel, G; Boulmedais, F; Strub, J M; Corti, A; Meyer, N; Guillot, M; Schaaf, P; Metz-Boutigue, M H A Pilot Study on Continuous Infusion of 4% Albumin in Critically Ill Patients: Impact on Nosocomial Infection via a Reduction Mechanism for Oxidized Substrates Article de journal Critical Care Explorations, 1 (9), 2019, (non). @article{653, title = {A Pilot Study on Continuous Infusion of 4% Albumin in Critically Ill Patients: Impact on Nosocomial Infection via a Reduction Mechanism for Oxidized Substrates}, author = {F Schneider and A -F Dureau and S Hellé and C Betscha and B Senger and G Cremel and F Boulmedais and J M Strub and A Corti and N Meyer and M Guillot and P Schaaf and M H Metz-Boutigue}, doi = {10.1097/CCE.0000000000000044}, year = {2019}, date = {2019-09-19}, journal = {Critical Care Explorations}, volume = {1}, number = {9}, note = {non}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Sabou, M; Doderer-Lang, C; Leyer, C; Konjic, A; Kubina, S; Lennon, S; Rohr, O; Viville, S; Cianférani, S; Candolfi, E; Pfaff, AW.; Brunet, J Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways Article de journal Cell Mol Life Sci. 2019 Sep 6., 2019. @article{650, title = {Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways}, author = {M Sabou and C Doderer-Lang and C Leyer and A Konjic and S Kubina and S Lennon and O Rohr and S Viville and S Cianférani and E Candolfi and AW. Pfaff and J Brunet}, doi = {10.1007/s00018-019-03267-2}, year = {2019}, date = {2019-09-06}, journal = {Cell Mol Life Sci. 2019 Sep 6.}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Hartmann, L; Botzanowski, T; Galibert, M; Jullian, M; l Chabrol, E; Zeder-Lutz, G; Kugler, V; Stojko, J; Strub, JM.; Ferry, G; Frankiewicz, L; Puget, K; Wagner, R; Cianférani, S; Boutin, JA. VHH characterization. Comparison of recombinant with chemically synthesized anti-HER2 VHH Article de journal Protein Sci., 28 (10), p. 1865-1879, 2019. @article{648, title = {VHH characterization. Comparison of recombinant with chemically synthesized anti-HER2 VHH}, author = {L Hartmann and T Botzanowski and M Galibert and M Jullian and E l Chabrol and G Zeder-Lutz and V Kugler and J Stojko and JM. Strub and G Ferry and L Frankiewicz and K Puget and R Wagner and S Cianférani and JA. Boutin}, doi = {10.1002/pro.3712}, year = {2019}, date = {2019-08-29}, journal = {Protein Sci.}, volume = {28}, number = {10}, pages = {1865-1879}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Chazarin, B; Ziemianin, A; Evans, A L; Meugnier, E; Loizon, E; Chery, I; Arnemo, J M; Swenson, J E; Gauquelin-Koch, G; Simon, C; Blanc, S; Lefai, E; Bertile, F Limited oxidative stress favors resistance to skeletal muscle atrophy in hibernating brown bears (Ursus arctos) Article de journal Antioxidants, 8 (9), p. 334, 2019, (2011/34). @article{647, title = {Limited oxidative stress favors resistance to skeletal muscle atrophy in hibernating brown bears (Ursus arctos)}, author = {B Chazarin and A Ziemianin and A L Evans and E Meugnier and E Loizon and I Chery and J M Arnemo and J E Swenson and G Gauquelin-Koch and C Simon and S Blanc and E Lefai and F Bertile}, doi = {10.3390/antiox8090334}, year = {2019}, date = {2019-08-22}, journal = {Antioxidants}, volume = {8}, number = {9}, pages = {334}, note = {2011/34}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Gervason, S; Larkem, D; Mansour, AB.; Botzanowski, T; Müller, CS.; Pecqueur, L; Pavec, Le G; Delaunay-Moisan, A; Brun, O; Agramunt, J; Grandas, A; Fontecave, M; Schünemann, V; Cianférani, S; Sizun, C; Tolédano, MB.; D'Autréaux, B Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide-processing functions of ferredoxin-2 and frataxin Article de journal Nat Commun., 10 (1), p. 3566, 2019. @article{638, title = {Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide-processing functions of ferredoxin-2 and frataxin}, author = {S Gervason and D Larkem and AB. Mansour and T Botzanowski and CS. Müller and L Pecqueur and G Le Pavec and A Delaunay-Moisan and O Brun and J Agramunt and A Grandas and M Fontecave and V Schünemann and S Cianférani and C Sizun and MB. Tolédano and B D'Autréaux}, doi = {10.1038/s41467-019-11470-9}, year = {2019}, date = {2019-08-08}, journal = {Nat Commun.}, volume = {10}, number = {1}, pages = {3566}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Sanchez, CP.; Cubel, Moliner S; Nyboer, B; Jankowska-Döllken, M; Schaeffer-Reiss, C; Ayoub, D; Planelles, G; Lanzer, M Phosphomimetic substitution at Ser-33 of the chloroquine resistance transporter PfCRT reconstitutes drug responses in Plasmodium falciparum Article de journal J Biol Chem., p. pii: jbc.RA119.009464., 2019. @article{646, title = {Phosphomimetic substitution at Ser-33 of the chloroquine resistance transporter PfCRT reconstitutes drug responses in Plasmodium falciparum}, author = {CP. Sanchez and S Moliner Cubel and B Nyboer and M Jankowska-Döllken and C Schaeffer-Reiss and D Ayoub and G Planelles and M Lanzer}, doi = {10.1074/jbc.RA119.009464}, year = {2019}, date = {2019-07-08}, journal = {J Biol Chem.}, pages = {pii: jbc.RA119.009464.}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Quque, M; Benhaim-Delarbre, M; Deneubourg, JL.; Sueur, C; Criscuolo, F; Bertile, F Division of labour in the black garden ant (Lasius niger) leads to three distinct proteomes Article de journal J Insect Physiol., 117 , p. 103907, 2019, (2015/29). @article{644, title = {Division of labour in the black garden ant (Lasius niger) leads to three distinct proteomes}, author = {M Quque and M Benhaim-Delarbre and JL. Deneubourg and C Sueur and F Criscuolo and F Bertile}, doi = {10.1016/j.jinsphys.2019.103907}, year = {2019}, date = {2019-06-27}, journal = {J Insect Physiol.}, volume = {117}, pages = {103907}, note = {2015/29}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Dalzon, B; Bons, J; Diemer, H; Collin-Faure, V; Marie-Desvergne, C; Dubosson, M; Cianferani, S; Carapito, C; Rabilloud, T A Proteomic View of Cellular Responses to Anticancer Quinoline-Copper Complexes Article de journal Proteomes, 7 (2), p. pii: E26, 2019. @article{639, title = {A Proteomic View of Cellular Responses to Anticancer Quinoline-Copper Complexes}, author = {B Dalzon and J Bons and H Diemer and V Collin-Faure and C Marie-Desvergne and M Dubosson and S Cianferani and C Carapito and T Rabilloud}, doi = {10.3390/proteomes7020026}, year = {2019}, date = {2019-06-24}, journal = {Proteomes}, volume = {7}, number = {2}, pages = {pii: E26}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Chazarin, B; Storey, KB.; Ziemianin, A; Chanon, S; Plumel, M; Chery, I; Durand, C; Evans, AL.; Arnemo, JM.; Zedrosser, A; Swenson, JE.; Gauquelin-Koch, G; Simon, C; Blanc, S; Lefai, E; Bertile, F Metabolic reprogramming involving glycolysis in the hibernating brown bear skeletal muscle Article de journal Front Zool., 16 , p. 12, 2019. @article{645, title = {Metabolic reprogramming involving glycolysis in the hibernating brown bear skeletal muscle}, author = {B Chazarin and KB. Storey and A Ziemianin and S Chanon and M Plumel and I Chery and C Durand and AL. Evans and JM. Arnemo and A Zedrosser and JE. Swenson and G Gauquelin-Koch and C Simon and S Blanc and E Lefai and F Bertile}, doi = {10.1186/s12983-019-0312-2}, year = {2019}, date = {2019-05-06}, journal = {Front Zool.}, volume = {16}, pages = {12}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Plumel, M; Dumont, S; Maes, P; Sandu, C; Felder-Scmittbuhl, M P; Challet, E; Bertile, F Circadian Analysis of the Mouse Cerebellum Proteome Article de journal International Journal of Molecular Sciences, 20 (8), p. 1852, 2019, (2012/26). @article{631, title = {Circadian Analysis of the Mouse Cerebellum Proteome}, author = {M Plumel and S Dumont and P Maes and C Sandu and M P Felder-Scmittbuhl and E Challet and F Bertile}, doi = {10.3390/ijms20081852}, year = {2019}, date = {2019-04-15}, journal = {International Journal of Molecular Sciences}, volume = {20}, number = {8}, pages = {1852}, note = {2012/26}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Giroud, S; Chery, I; F., Bertile;; Bertrand-Michel, J; Tascher, G; Gauquelin-Koch, G; Arnemo, J M; Swenson, J E; Singh, N V; Lefai, E; Evans, A L; Simon, C; Blanc, S Lipidomics Reveals Seasonal Shifts in a Large-Bodied Hibernator, the Brown Bear Article de journal Front Physiol., 10 , p. 389, 2019, (2011/30). @article{630, title = {Lipidomics Reveals Seasonal Shifts in a Large-Bodied Hibernator, the Brown Bear}, author = {S Giroud and I Chery and Bertile; F. and J Bertrand-Michel and G Tascher and G Gauquelin-Koch and J M Arnemo and J E Swenson and N V Singh and E Lefai and A L Evans and C Simon and S Blanc}, doi = {10.3389/fphys.2019.00389}, year = {2019}, date = {2019-04-12}, journal = {Front Physiol.}, volume = {10}, pages = {389}, note = {2011/30}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Camus, M; Hirschi, S; Prevot, G; Chenard, M P; Mal, H; Stern, M; Reynaud-Gaubert, M; Gilhodes, J; Burlet-Schiltz, O; Brousset, P; Colombat, M Proteomic evidence of specific IGKV1-8 association with cystic lung light chain deposition disease Article de journal Blood, 133 (26), p. 2741–2744, 2019. @article{pmid30967366, title = {Proteomic evidence of specific IGKV1-8 association with cystic lung light chain deposition disease}, author = {M Camus and S Hirschi and G Prevot and M P Chenard and H Mal and M Stern and M Reynaud-Gaubert and J Gilhodes and O Burlet-Schiltz and P Brousset and M Colombat}, doi = {10.1182/blood.2019898577}, year = {2019}, date = {2019-04-09}, journal = {Blood}, volume = {133}, number = {26}, pages = {2741--2744}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Chabert, M; Rousset, X; Colombat, M; Lacasa, M; Kakanakou, H; Bourderioux, M; Brousset, P; Burlet-Schiltz, O; Liepnieks, J J; Kluve-Beckerman, B; Lambert, G; Châtelet, F P; Benson, M D; Kalopissis, A D A transgenic mouse model reproduces human hereditary systemic amyloidosis Article de journal Kidney Int., 96 (3), p. 628–641, 2019. @article{pmid31200944, title = {A transgenic mouse model reproduces human hereditary systemic amyloidosis}, author = {M Chabert and X Rousset and M Colombat and M Lacasa and H Kakanakou and M Bourderioux and P Brousset and O Burlet-Schiltz and J J Liepnieks and B Kluve-Beckerman and G Lambert and F P Châtelet and M D Benson and A D Kalopissis}, doi = {10.1016/j.kint.2019.03.013}, year = {2019}, date = {2019-03-28}, journal = {Kidney Int.}, volume = {96}, number = {3}, pages = {628--641}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Bons, J; Macron, C; Aude-Garcia, C; Vaca-Jacome, SA.; Rompais, M; Cianférani, S; Carapito, C; Rabilloud, T A Combined N-terminomics and Shotgun Proteomics Approach to Investigate the Responses of Human Cells to Rapamycin and Zinc at the Mitochondrial Level Article de journal Mol Cell Proteomics, 18 (6), p. 1085-1095, 2019. @article{640, title = {A Combined N-terminomics and Shotgun Proteomics Approach to Investigate the Responses of Human Cells to Rapamycin and Zinc at the Mitochondrial Level}, author = {J Bons and C Macron and C Aude-Garcia and SA. Vaca-Jacome and M Rompais and S Cianférani and C Carapito and T Rabilloud}, doi = {10.1074/mcp.RA118.001269}, year = {2019}, date = {2019-03-15}, journal = {Mol Cell Proteomics}, volume = {18}, number = {6}, pages = {1085-1095}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Muller, L; Fornecker, L; Cianferani, S; Carapito, C Tube-Gel: A Fast and Effective Sample Preparation Method for High-Throughput Quantitative Proteomics Article de journal Methods Mol Biol., 1959 , p. 123-127, 2019. @article{632, title = {Tube-Gel: A Fast and Effective Sample Preparation Method for High-Throughput Quantitative Proteomics}, author = {L Muller and L Fornecker and S Cianferani and C Carapito}, doi = {10.1007/978-1-4939-9164-8_8}, year = {2019}, date = {2019-03-10}, journal = {Methods Mol Biol.}, volume = {1959}, pages = {123-127}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Pichereaux, C; Laurent, E A; Gargaros, A; Viudes, S; Durieu, C; Lamaze, T; Grieu, P; Burlet-Schiltz, O J Proteomics, 200 , p. 28–39, 2019. @article{pmid30862563, title = {Analysis of durum wheat proteome changes under marine and fungal biostimulant treatments using large-scale quantitative proteomics: A useful dataset of durum wheat proteins}, author = {C Pichereaux and E A Laurent and A Gargaros and S Viudes and C Durieu and T Lamaze and P Grieu and O Burlet-Schiltz}, doi = {10.1016/j.jprot.2019.03.003}, year = {2019}, date = {2019-03-09}, journal = {J Proteomics}, volume = {200}, pages = {28--39}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Tascher, G; Burban, A; Camus, S; Plumel, M; Chanon, S; Guevel, Le R; Shevchenko, V; Dorsselaer, Van A; Lefai, E; Guguen-Guillouzo, C; Bertile, F In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes Article de journal Cells, 8 (2), p. 192, 2019, (2012/20). @article{629, title = {In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes}, author = {G Tascher and A Burban and S Camus and M Plumel and S Chanon and R Le Guevel and V Shevchenko and A Van Dorsselaer and E Lefai and C Guguen-Guillouzo and F Bertile}, doi = {10.3390/cells8020192}, year = {2019}, date = {2019-02-21}, journal = {Cells}, volume = {8}, number = {2}, pages = {192}, note = {2012/20}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Beck, A; D'Atri, V; Ehkirch, A; Fekete, S; Hernandez-Alba, O; Gahoual, R; Leize-Wagner, E; François, Y; Guillarme, D; Cianférani, S Cutting-edge multi-level analytical and structural characterization of antibody-drug conjugates: present and future Article de journal Expert Rev Proteomics., 16 (4), p. 337-362., 2019, (review). @article{633, title = {Cutting-edge multi-level analytical and structural characterization of antibody-drug conjugates: present and future}, author = {A Beck and V D'Atri and A Ehkirch and S Fekete and O Hernandez-Alba and R Gahoual and E Leize-Wagner and Y François and D Guillarme and S Cianférani}, doi = {10.1080/14789450.2019.1578215}, year = {2019}, date = {2019-02-18}, journal = {Expert Rev Proteomics.}, volume = {16}, number = {4}, pages = {337-362.}, note = {review}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Locard-Paulet, M; Parra, J; Albigot, R; Mouton-Barbosa, E; Bardi, L; Burlet-Schiltz, O; Marcoux, J VisioProt-MS: interactive 2D maps from intact protein mass spectrometry Article de journal Bioinformatics, 35 (4), p. 679–681, 2019. @article{pmid30084957, title = {VisioProt-MS: interactive 2D maps from intact protein mass spectrometry}, author = {M Locard-Paulet and J Parra and R Albigot and E Mouton-Barbosa and L Bardi and O Burlet-Schiltz and J Marcoux}, doi = {10.1093/bioinformatics/bty680}, year = {2019}, date = {2019-02-15}, journal = {Bioinformatics}, volume = {35}, number = {4}, pages = {679--681}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Strassel, C; Magiera, MM.; Dupuis, A; Batzenschlager, M; Hovasse, A; Pleines, I; Guéguen, P; Eckly, A; Moog, S; Mallo, L; Kimmerlin, Q; Chappaz, S; Strub, JM.; Kathiresan, N; de la Salle, H; Dorsselaer, Van A; Ferec, C; Py, JY.; Gachet, C; Schaeffer-Reiss, C; Kile, BT.; Janke, C; Lanza, F An essential role for α4A-tubulin in platelet biogenesis Article de journal Life Sci Alliance, 2 (1), p. pii: e201900309., 2019. @article{637, title = {An essential role for α4A-tubulin in platelet biogenesis}, author = {C Strassel and MM. Magiera and A Dupuis and M Batzenschlager and A Hovasse and I Pleines and P Guéguen and A Eckly and S Moog and L Mallo and Q Kimmerlin and S Chappaz and JM. Strub and N Kathiresan and H de la Salle and A Van Dorsselaer and C Ferec and JY. Py and C Gachet and C Schaeffer-Reiss and BT. Kile and C Janke and F Lanza}, doi = {10.26508/lsa.201900309}, year = {2019}, date = {2019-02-13}, journal = {Life Sci Alliance}, volume = {2}, number = {1}, pages = {pii: e201900309.}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Hyenne, V; Ghoroghi, S; Collot, M; Bons, J; Follain, G; Harlepp, S; Mary, B; Bauer, J; Mercier, L; Busnelli, I; Lefebvre, O; Fekonja, N; Garcia-Leon, MJ.; Machado, P; Delalande, F; López, AA.; Silva, SG.; Verweij, FJ.; van Niel, G; Djouad, F; Peinado, H; Carapito, C; Klymchenko, AS.; Goetz, JG. Studying the Fate of Tumor Extracellular Vesicles at High Spatiotemporal Resolution Using the Zebrafish Embryo Article de journal Dev Cell., 48 (4), p. 554-572.e7, 2019. @article{635, title = {Studying the Fate of Tumor Extracellular Vesicles at High Spatiotemporal Resolution Using the Zebrafish Embryo}, author = {V Hyenne and S Ghoroghi and M Collot and J Bons and G Follain and S Harlepp and B Mary and J Bauer and L Mercier and I Busnelli and O Lefebvre and N Fekonja and MJ. Garcia-Leon and P Machado and F Delalande and AA. López and SG. Silva and FJ. Verweij and G van Niel and F Djouad and H Peinado and C Carapito and AS. Klymchenko and JG. Goetz}, doi = {10.1016/j.devcel.2019.01.014}, year = {2019}, date = {2019-02-07}, journal = {Dev Cell.}, volume = {48}, number = {4}, pages = {554-572.e7}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Menneteau, T; Fabre, B; Garrigues, L; Stella, A; Zivkovic, D; Roux-Dalvai, F; Mouton-Barbosa, E; Beau, M; Renoud, M L; Amalric, F; Sensébé, L; Gonzalez-de-Peredo, A; Ader, I; Burlet-Schiltz, O; Bousquet, M P Mass Spectrometry-based Absolute Quantification of 20S Proteasome Status for Controlled Ex-vivo Expansion of Ħuman Adipose-derived Mesenchymal Stromal/Stem Cells Article de journal Mol. Cell Proteomics, 18 (4), p. 744–759, 2019. @article{pmid30700495, title = {Mass Spectrometry-based Absolute Quantification of 20S Proteasome Status for Controlled Ex-vivo Expansion of Ħuman Adipose-derived Mesenchymal Stromal/Stem Cells}, author = {T Menneteau and B Fabre and L Garrigues and A Stella and D Zivkovic and F Roux-Dalvai and E Mouton-Barbosa and M Beau and M L Renoud and F Amalric and L Sensébé and A Gonzalez-de-Peredo and I Ader and O Burlet-Schiltz and M P Bousquet}, doi = {10.1074/mcp.RA118.000958}, year = {2019}, date = {2019-01-30}, journal = {Mol. Cell Proteomics}, volume = {18}, number = {4}, pages = {744--759}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Fornecker, LM.; Muller, L; Bertrand, F; Paul, N; Pichot, A; Herbrecht, R; Chenard, MP.; Mauvieux, L; Vallat, L; Bahram, S; Cianférani, S; Carapito, R; Carapito, C Multi-omics dataset to decipher the complexity of drug resistance in diffuse large B-cell lymphoma Article de journal Sci Rep., 9 (1), p. 895, 2019. @article{628, title = {Multi-omics dataset to decipher the complexity of drug resistance in diffuse large B-cell lymphoma}, author = {LM. Fornecker and L Muller and F Bertrand and N Paul and A Pichot and R Herbrecht and MP. Chenard and L Mauvieux and L Vallat and S Bahram and S Cianférani and R Carapito and C Carapito}, doi = {10.1038/s41598-018-37273-4}, year = {2019}, date = {2019-01-29}, journal = {Sci Rep.}, volume = {9}, number = {1}, pages = {895}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Aniort, J; Stella, A; Philipponnet, C; Poyet, A; Polge, C; Claustre, A; Combaret, L; B?chet, D; Attaix, D; Boisgard, S; Filaire, M; Rosset, E; Burlet-Schiltz, O; Heng, A E; Taillandier, D Muscle wasting in patients with end-stage renal disease or early-stage lung cancer: common mechanisms at work Article de journal J Cachexia Sarcopenia Muscle, 10 (2), p. 323–337, 2019. @article{pmid30697967, title = {Muscle wasting in patients with end-stage renal disease or early-stage lung cancer: common mechanisms at work}, author = {J Aniort and A Stella and C Philipponnet and A Poyet and C Polge and A Claustre and L Combaret and D B?chet and D Attaix and S Boisgard and M Filaire and E Rosset and O Burlet-Schiltz and A E Heng and D Taillandier}, doi = {0.1002/jcsm.12376}, year = {2019}, date = {2019-01-29}, journal = {J Cachexia Sarcopenia Muscle}, volume = {10}, number = {2}, pages = {323--337}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Groysbeck, N; Stoessel, A; Donzeau, M; da Silva, EC.; Lehmann, M; Strub, JM.; Cianferani, S; Dembélé, K; Zuber, G Synthesis and biological evaluation of 2.4 nm thiolate-protected gold nanoparticles conjugated to Cetuximab for targeting glioblastoma cancer cells via the EGFR Article de journal Nanotechnology, 30 (18), p. 184005., 2019. @article{634, title = {Synthesis and biological evaluation of 2.4 nm thiolate-protected gold nanoparticles conjugated to Cetuximab for targeting glioblastoma cancer cells via the EGFR}, author = {N Groysbeck and A Stoessel and M Donzeau and EC. da Silva and M Lehmann and JM. Strub and S Cianferani and K Dembélé and G Zuber}, doi = { 10.1088/1361-6528/aaff0a}, year = {2019}, date = {2019-01-16}, journal = {Nanotechnology}, volume = {30}, number = {18}, pages = {184005.}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Rochel, N; Krucker, C; Coutos-Thévenot, L; Osz, J; Zhang, R; Guyon, E; Zita, W; Vanthong, S; Hernandez-Alba, O; Bourguet, M; Badawy, Al K; Dufour, F; Peluso-Iltis, C; Heckler-Beji, S; Dejaegere, A; Kamoun, A; de Reyniès, A; Neuzillet, Y; Rebouissou, S; Béraud, C; Lang, H; Massfelder, T; Allory, Y; Cianférani, S; Stote, R H; Radvanyi, F; Bernard-Pierrot, I Recurrent activating mutations of PPARγ associated with luminal bladder tumors Article de journal Nature Communications, 10 (1), p. 253, 2019. @article{627, title = {Recurrent activating mutations of PPARγ associated with luminal bladder tumors}, author = {N Rochel and C Krucker and L Coutos-Thévenot and J Osz and R Zhang and E Guyon and W Zita and S Vanthong and O Hernandez-Alba and M Bourguet and K Al Badawy and F Dufour and C Peluso-Iltis and S Heckler-Beji and A Dejaegere and A Kamoun and A de Reyniès and Y Neuzillet and S Rebouissou and C Béraud and H Lang and T Massfelder and Y Allory and S Cianférani and R H Stote and F Radvanyi and I Bernard-Pierrot}, doi = {10.1038/s41467-018-08157-y}, year = {2019}, date = {2019-01-16}, journal = {Nature Communications}, volume = {10}, number = {1}, pages = {253}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Niazi, AK.; Bariat, L; Riondet, C; Carapito, C; Mhamdi, A; Noctor, G; Reichheld, JP. Cytosolic Isocitrate Dehydrogenase from Arabidopsis thaliana Is Regulated by Glutathionylation Article de journal Antioxidants (Basel), 8 (1), p. pii: E16., 2019. @article{636, title = {Cytosolic Isocitrate Dehydrogenase from Arabidopsis thaliana Is Regulated by Glutathionylation}, author = {AK. Niazi and L Bariat and C Riondet and C Carapito and A Mhamdi and G Noctor and JP. Reichheld}, doi = {10.3390/antiox8010016}, year = {2019}, date = {2019-01-08}, journal = {Antioxidants (Basel)}, volume = {8}, number = {1}, pages = {pii: E16.}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
è, Agn; Tillet, Emmanuelle; Ricard, Nicolas; Ouarné, Marie; Mallet, Christine; Belmudes, Lucid; Couté, Yohann; Boillot, Olivier; Scoazec, Jean-Yves; Bailly, Sabine; Feige, Jean-Jacques Bone Morphogenetic Protein 9 Is a Paracrine Factor Controlling Liver Sinusoidal Endothelial Cell Fenestration and Protecting Against Hepatic Fibrosis Article de journal Hepatology (Baltimore, Md.), 70 (4), p. 1392–1408, 2019, ISSN: 1527-3350. @article{desroches-castan_bone_2019, title = {Bone Morphogenetic Protein 9 Is a Paracrine Factor Controlling Liver Sinusoidal Endothelial Cell Fenestration and Protecting Against Hepatic Fibrosis}, author = {Agn{è}s Desroches-Castan and Emmanuelle Tillet and Nicolas Ricard and Marie Ouarné and Christine Mallet and Lucid Belmudes and Yohann Couté and Olivier Boillot and Jean-Yves Scoazec and Sabine Bailly and Jean-Jacques Feige}, doi = {10.1002/hep.30655}, issn = {1527-3350}, year = {2019}, date = {2019-01-01}, journal = {Hepatology (Baltimore, Md.)}, volume = {70}, number = {4}, pages = {1392--1408}, abstract = {Bone morphogenetic protein 9 (BMP9) is a circulating factor produced by hepatic stellate cells that plays a critical role in vascular quiescence through its endothelial receptor activin receptor-like kinase 1 (ALK1). Mutations in the gene encoding ALK1 cause hereditary hemorrhagic telangiectasia type 2, a rare genetic disease presenting hepatic vessel malformations. Variations of both the circulating levels and the hepatic mRNA levels of BMP9 have been recently associated with various forms of hepatic fibrosis. However, the molecular mechanism that links BMP9 with liver diseases is still unknown. Here, we report that Bmp9 gene deletion in 129/Ola mice triggers hepatic perisinusoidal fibrosis that was detectable from 15 weeks of age. An inflammatory response appeared within the same time frame as fibrosis, whereas sinusoidal vessel dilation developed later on. Proteomic and mRNA analyses of primary liver sinusoidal endothelial cells (LSECs) both revealed that the expression of the LSEC-specifying transcription factor GATA-binding protein 4 was strongly reduced in Bmp9 gene knockout (Bmp9-KO) mice as compared with wild-type mice. LSECs from Bmp9-KO mice also lost the expression of several terminal differentiation markers (Lyve1, Stab1, Stab2, Ehd3, Cd209b, eNos, Maf, Plvap). They gained CD34 expression and deposited a basal lamina, indicating that they were capillarized. Another main characteristic of differentiated LSECs is the presence of permeable fenestrae. LSECs from Bmp9-KO mice had a significantly reduced number of fenestrae. This was already observable in 2-week-old pups. Moreover, we could show that addition of BMP9 to primary cultures of LSECs prevented the loss of their fenestrae and maintained the expression levels of Gata4 and Plvap. Conclusion: Taken together, our observations show that BMP9 is a key paracrine regulator of liver homeostasis, controlling LSEC fenestration and protecting against perivascular hepatic fibrosis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bone morphogenetic protein 9 (BMP9) is a circulating factor produced by hepatic stellate cells that plays a critical role in vascular quiescence through its endothelial receptor activin receptor-like kinase 1 (ALK1). Mutations in the gene encoding ALK1 cause hereditary hemorrhagic telangiectasia type 2, a rare genetic disease presenting hepatic vessel malformations. Variations of both the circulating levels and the hepatic mRNA levels of BMP9 have been recently associated with various forms of hepatic fibrosis. However, the molecular mechanism that links BMP9 with liver diseases is still unknown. Here, we report that Bmp9 gene deletion in 129/Ola mice triggers hepatic perisinusoidal fibrosis that was detectable from 15 weeks of age. An inflammatory response appeared within the same time frame as fibrosis, whereas sinusoidal vessel dilation developed later on. Proteomic and mRNA analyses of primary liver sinusoidal endothelial cells (LSECs) both revealed that the expression of the LSEC-specifying transcription factor GATA-binding protein 4 was strongly reduced in Bmp9 gene knockout (Bmp9-KO) mice as compared with wild-type mice. LSECs from Bmp9-KO mice also lost the expression of several terminal differentiation markers (Lyve1, Stab1, Stab2, Ehd3, Cd209b, eNos, Maf, Plvap). They gained CD34 expression and deposited a basal lamina, indicating that they were capillarized. Another main characteristic of differentiated LSECs is the presence of permeable fenestrae. LSECs from Bmp9-KO mice had a significantly reduced number of fenestrae. This was already observable in 2-week-old pups. Moreover, we could show that addition of BMP9 to primary cultures of LSECs prevented the loss of their fenestrae and maintained the expression levels of Gata4 and Plvap. Conclusion: Taken together, our observations show that BMP9 is a key paracrine regulator of liver homeostasis, controlling LSEC fenestration and protecting against perivascular hepatic fibrosis. |
Azevedo, Jacinthe; Picart, Claire; Dureau, Laurent; Pontier, Dominique; Jaquinod-Kieffer, Sylvie; Hakimi, Mohamed-Ali; Lagrange, Thierry UAP56 associates with DRM2 and is localized to chromatin in Arabidopsis Article de journal FEBS open bio, 9 (5), p. 973–985, 2019, ISSN: 2211-5463. @article{azevedo_uap56_2019, title = {UAP56 associates with DRM2 and is localized to chromatin in Arabidopsis}, author = {Jacinthe Azevedo and Claire Picart and Laurent Dureau and Dominique Pontier and Sylvie Jaquinod-Kieffer and Mohamed-Ali Hakimi and Thierry Lagrange}, doi = {10.1002/2211-5463.12627}, issn = {2211-5463}, year = {2019}, date = {2019-01-01}, journal = {FEBS open bio}, volume = {9}, number = {5}, pages = {973--985}, abstract = {Repeated sequence expression and transposable element mobilization are tightly controlled by multilayer processes, which include DNA 5'-cytosine methylation. The RNA-directed DNA methylation (RdDM) pathway, which uses siRNAs to guide sequence-specific directed DNA methylation, emerged specifically in plants. RdDM ensures DNA methylation maintenance on asymmetric CHH sites and specifically initiates de novo methylation in all cytosine sequence contexts through the action of DRM DNA methyltransferases, of which DRM2 is the most prominent. The RdDM pathway has been well described, but how DRM2 is recruited onto DNA targets and associates with other RdDM factors remains unknown. To address these questions, we developed biochemical approaches to allow the identification of factors that may escape genetic screens, such as proteins encoded by multigenic families. Through both conventional and affinity purification of DRM2, we identified DEAD box RNA helicases U2AF56 Associated Protein 56 (UAP56a/b), which are widespread among eukaryotes, as new DRM2 partners. We have shown that, similar to DRM2 and other RdDM actors, UAP56 has chromatin-associated protein properties. We confirmed this association both in vitro and in vivo in reproductive tissues. In addition, our experiments also suggest that UAP56 may exhibit differential distribution in cells depending on plant organ. While originally identified for its role in splicing, our study suggests that UAP56 may also have other roles, and our findings allow us to initiate discussion about its potential role in the RdDM pathway.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Repeated sequence expression and transposable element mobilization are tightly controlled by multilayer processes, which include DNA 5'-cytosine methylation. The RNA-directed DNA methylation (RdDM) pathway, which uses siRNAs to guide sequence-specific directed DNA methylation, emerged specifically in plants. RdDM ensures DNA methylation maintenance on asymmetric CHH sites and specifically initiates de novo methylation in all cytosine sequence contexts through the action of DRM DNA methyltransferases, of which DRM2 is the most prominent. The RdDM pathway has been well described, but how DRM2 is recruited onto DNA targets and associates with other RdDM factors remains unknown. To address these questions, we developed biochemical approaches to allow the identification of factors that may escape genetic screens, such as proteins encoded by multigenic families. Through both conventional and affinity purification of DRM2, we identified DEAD box RNA helicases U2AF56 Associated Protein 56 (UAP56a/b), which are widespread among eukaryotes, as new DRM2 partners. We have shown that, similar to DRM2 and other RdDM actors, UAP56 has chromatin-associated protein properties. We confirmed this association both in vitro and in vivo in reproductive tissues. In addition, our experiments also suggest that UAP56 may exhibit differential distribution in cells depending on plant organ. While originally identified for its role in splicing, our study suggests that UAP56 may also have other roles, and our findings allow us to initiate discussion about its potential role in the RdDM pathway. |
Vandenbrouck, Yves; Christiany, David; Combes, Florence; Loux, Valentin; Brun, Virginie Bioinformatics Tools and Workflow to Select Blood Biomarkers for Early Cancer Diagnosis: An Application to Pancreatic Cancer Article de journal Proteomics, 19 (21-22), p. e1800489, 2019, ISSN: 1615-9861. @article{vandenbrouck_bioinformatics_2019, title = {Bioinformatics Tools and Workflow to Select Blood Biomarkers for Early Cancer Diagnosis: An Application to Pancreatic Cancer}, author = {Yves Vandenbrouck and David Christiany and Florence Combes and Valentin Loux and Virginie Brun}, doi = {10.1002/pmic.201800489}, issn = {1615-9861}, year = {2019}, date = {2019-01-01}, journal = {Proteomics}, volume = {19}, number = {21-22}, pages = {e1800489}, abstract = {Secretome proteomics for the discovery of cancer biomarkers holds great potential to improve early cancer diagnosis. A knowledge-based approach relying on mechanistic criteria related to the type of cancer should help to identify candidates from available "omics" information. With the aim of accelerating the discovery process for novel biomarkers, a set of tools is developed and made available via a Galaxy-based instance to assist end-users biologists. These implemented tools proceed by a step-by-step strategy to mine transcriptomics and proteomics databases for information relating to tissue specificity, allow the selection of proteins that are part of the secretome, and combine this information with proteomics datasets to rank the most promising candidate biomarkers for early cancer diagnosis. Using pancreatic cancer as a case study, this strategy produces a list of 24 candidate biomarkers suitable for experimental assessment by MS-based proteomics. Among these proteins, three (SYCN, REG1B, and PRSS2) were previously reported as circulating candidate biomarkers of pancreatic cancer. Here, further refinement of this list allows to prioritize 14 candidate biomarkers along with their associated proteotypic peptides for further investigation, using targeted MS-based proteomics. The bioinformatics tools and the workflow implementing this strategy for the selection of candidate biomarkers are freely accessible at http://www.proteore.org.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Secretome proteomics for the discovery of cancer biomarkers holds great potential to improve early cancer diagnosis. A knowledge-based approach relying on mechanistic criteria related to the type of cancer should help to identify candidates from available "omics" information. With the aim of accelerating the discovery process for novel biomarkers, a set of tools is developed and made available via a Galaxy-based instance to assist end-users biologists. These implemented tools proceed by a step-by-step strategy to mine transcriptomics and proteomics databases for information relating to tissue specificity, allow the selection of proteins that are part of the secretome, and combine this information with proteomics datasets to rank the most promising candidate biomarkers for early cancer diagnosis. Using pancreatic cancer as a case study, this strategy produces a list of 24 candidate biomarkers suitable for experimental assessment by MS-based proteomics. Among these proteins, three (SYCN, REG1B, and PRSS2) were previously reported as circulating candidate biomarkers of pancreatic cancer. Here, further refinement of this list allows to prioritize 14 candidate biomarkers along with their associated proteotypic peptides for further investigation, using targeted MS-based proteomics. The bioinformatics tools and the workflow implementing this strategy for the selection of candidate biomarkers are freely accessible at http://www.proteore.org. |
Guillot, Laetitia; Delage, Ludovic; Viari, Alain; Vandenbrouck, Yves; Com, Emmanuelle; Ritter, Andrés; Lavigne, Régis; Marie, Dominique; Peterlongo, Pierre; Potin, Philippe; Pineau, Charles Peptimapper: proteogenomics workflow for the expert annotation of eukaryotic genomes Article de journal BMC genomics, 20 (1), p. 56, 2019, ISSN: 1471-2164. @article{guillot_peptimapper:_2019, title = {Peptimapper: proteogenomics workflow for the expert annotation of eukaryotic genomes}, author = {Laetitia Guillot and Ludovic Delage and Alain Viari and Yves Vandenbrouck and Emmanuelle Com and Andrés Ritter and Régis Lavigne and Dominique Marie and Pierre Peterlongo and Philippe Potin and Charles Pineau}, doi = {10.1186/s12864-019-5431-9}, issn = {1471-2164}, year = {2019}, date = {2019-01-01}, journal = {BMC genomics}, volume = {20}, number = {1}, pages = {56}, abstract = {BACKGROUND: Accurate structural annotation of genomes is still a challenge, despite the progress made over the past decade. The prediction of gene structure remains difficult, especially for eukaryotic species, and is often erroneous and incomplete. We used a proteogenomics strategy, taking advantage of the combination of proteomics datasets and bioinformatics tools, to identify novel protein coding-genes and splice isoforms, assign correct start sites, and validate predicted exons and genes. RESULTS: Our proteogenomics workflow, Peptimapper, was applied to the genome annotation of Ectocarpus sp., a key reference genome for both the brown algal lineage and stramenopiles. We generated proteomics data from various life cycle stages of Ectocarpus sp. strains and sub-cellular fractions using a shotgun approach. First, we directly generated peptide sequence tags (PSTs) from the proteomics data. Second, we mapped PSTs onto the translated genomic sequence. Closely located hits (i.e., PSTs locations on the genome) were then clustered to detect potential coding regions based on parameters optimized for the organism. Third, we evaluated each cluster and compared it to gene predictions from existing conventional genome annotation approaches. Finally, we integrated cluster locations into GFF files to use a genome viewer. We identified two potential novel genes, a ribosomal protein L22 and an aryl sulfotransferase and corrected the gene structure of a dihydrolipoamide acetyltransferase. We experimentally validated the results by RT-PCR and using transcriptomics data. CONCLUSIONS: Peptimapper is a complementary tool for the expert annotation of genomes. It is suitable for any organism and is distributed through a Docker image available on two public bioinformatics docker repositories: Docker Hub and BioShaDock. This workflow is also accessible through the Galaxy framework and for use by non-computer scientists at https://galaxy.protim.eu . Data are available via ProteomeXchange under identifier PXD010618.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Accurate structural annotation of genomes is still a challenge, despite the progress made over the past decade. The prediction of gene structure remains difficult, especially for eukaryotic species, and is often erroneous and incomplete. We used a proteogenomics strategy, taking advantage of the combination of proteomics datasets and bioinformatics tools, to identify novel protein coding-genes and splice isoforms, assign correct start sites, and validate predicted exons and genes. RESULTS: Our proteogenomics workflow, Peptimapper, was applied to the genome annotation of Ectocarpus sp., a key reference genome for both the brown algal lineage and stramenopiles. We generated proteomics data from various life cycle stages of Ectocarpus sp. strains and sub-cellular fractions using a shotgun approach. First, we directly generated peptide sequence tags (PSTs) from the proteomics data. Second, we mapped PSTs onto the translated genomic sequence. Closely located hits (i.e., PSTs locations on the genome) were then clustered to detect potential coding regions based on parameters optimized for the organism. Third, we evaluated each cluster and compared it to gene predictions from existing conventional genome annotation approaches. Finally, we integrated cluster locations into GFF files to use a genome viewer. We identified two potential novel genes, a ribosomal protein L22 and an aryl sulfotransferase and corrected the gene structure of a dihydrolipoamide acetyltransferase. We experimentally validated the results by RT-PCR and using transcriptomics data. CONCLUSIONS: Peptimapper is a complementary tool for the expert annotation of genomes. It is suitable for any organism and is distributed through a Docker image available on two public bioinformatics docker repositories: Docker Hub and BioShaDock. This workflow is also accessible through the Galaxy framework and for use by non-computer scientists at https://galaxy.protim.eu . Data are available via ProteomeXchange under identifier PXD010618. |
Legendre, Matthieu; Alempic, Jean-Marie; è, Nad; Lartigue, Audrey; Jeudy, Sandra; Poirot, Olivier; Ta, Ngan Thi; Nin, Sébastien; Couté, Yohann; Abergel, Chantal; Claverie, Jean-Michel Pandoravirus Celtis Illustrates the Microevolution Processes at Work in the Giant Pandoraviridae Genomes Article de journal Frontiers in Microbiology, 10 , p. 430, 2019, ISSN: 1664-302X. @article{legendre_pandoravirus_2019, title = {Pandoravirus Celtis Illustrates the Microevolution Processes at Work in the Giant Pandoraviridae Genomes}, author = {Matthieu Legendre and Jean-Marie Alempic and Nad{è}ge Philippe and Audrey Lartigue and Sandra Jeudy and Olivier Poirot and Ngan Thi Ta and Sébastien Nin and Yohann Couté and Chantal Abergel and Jean-Michel Claverie}, doi = {10.3389/fmicb.2019.00430}, issn = {1664-302X}, year = {2019}, date = {2019-01-01}, journal = {Frontiers in Microbiology}, volume = {10}, pages = {430}, abstract = {With genomes of up to 2.7 Mb propagated in $mu$m-long oblong particles and initially predicted to encode more than 2000 proteins, members of the Pandoraviridae family display the most extreme features of the known viral world. The mere existence of such giant viruses raises fundamental questions about their origin and the processes governing their evolution. A previous analysis of six newly available isolates, independently confirmed by a study including three others, established that the Pandoraviridae pan-genome is open, meaning that each new strain exhibits protein-coding genes not previously identified in other family members. With an average increment of about 60 proteins, the gene repertoire shows no sign of reaching a limit and remains largely coding for proteins without recognizable homologs in other viruses or cells (ORFans). To explain these results, we proposed that most new protein-coding genes were created de novo, from pre-existing non-coding regions of the G+C rich pandoravirus genomes. The comparison of the gene content of a new isolate, pandoravirus celtis, closely related (96% identical genome) to the previously described p. quercus is now used to test this hypothesis by studying genomic changes in a microevolution range. Our results confirm that the differences between these two similar gene contents mostly consist of protein-coding genes without known homologs, with statistical signatures close to that of intergenic regions. These newborn proteins are under slight negative selection, perhaps to maintain stable folds and prevent protein aggregation pending the eventual emergence of fitness-increasing functions. Our study also unraveled several insertion events mediated by a transposase of the hAT family, 3 copies of which are found in p. celtis and are presumably active. Members of the Pandoraviridae are presently the first viruses known to encode this type of transposase.}, keywords = {}, pubstate = {published}, tppubtype = {article} } With genomes of up to 2.7 Mb propagated in $mu$m-long oblong particles and initially predicted to encode more than 2000 proteins, members of the Pandoraviridae family display the most extreme features of the known viral world. The mere existence of such giant viruses raises fundamental questions about their origin and the processes governing their evolution. A previous analysis of six newly available isolates, independently confirmed by a study including three others, established that the Pandoraviridae pan-genome is open, meaning that each new strain exhibits protein-coding genes not previously identified in other family members. With an average increment of about 60 proteins, the gene repertoire shows no sign of reaching a limit and remains largely coding for proteins without recognizable homologs in other viruses or cells (ORFans). To explain these results, we proposed that most new protein-coding genes were created de novo, from pre-existing non-coding regions of the G+C rich pandoravirus genomes. The comparison of the gene content of a new isolate, pandoravirus celtis, closely related (96% identical genome) to the previously described p. quercus is now used to test this hypothesis by studying genomic changes in a microevolution range. Our results confirm that the differences between these two similar gene contents mostly consist of protein-coding genes without known homologs, with statistical signatures close to that of intergenic regions. These newborn proteins are under slight negative selection, perhaps to maintain stable folds and prevent protein aggregation pending the eventual emergence of fitness-increasing functions. Our study also unraveled several insertion events mediated by a transposase of the hAT family, 3 copies of which are found in p. celtis and are presumably active. Members of the Pandoraviridae are presently the first viruses known to encode this type of transposase. |
Do, Le Duy; Gupton, Stephanie L; Tanji, Kunikazu; Bastien, Joubert; è, Sabine Brugi; Couté, Yohann; Quadrio, Isabelle; Rogemond, Veronique; Fabien, Nicole; Desestret, Virginie; Honnorat, Jerome TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration Article de journal Cerebellum (London, England), 18 (2), p. 245–254, 2019, ISSN: 1473-4230. @article{do_trim9_2019, title = {TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration}, author = {Le Duy Do and Stephanie L Gupton and Kunikazu Tanji and Joubert Bastien and Sabine Brugi{è}re and Yohann Couté and Isabelle Quadrio and Veronique Rogemond and Nicole Fabien and Virginie Desestret and Jerome Honnorat}, doi = {10.1007/s12311-018-0987-5}, issn = {1473-4230}, year = {2019}, date = {2019-01-01}, journal = {Cerebellum (London, England)}, volume = {18}, number = {2}, pages = {245--254}, abstract = {To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67, and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, 36 patients with lung adenocarcinoma and PNS, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases. We found Abs targeting TRIM9 and TRIM67 at high concentration in the serum and the cerebrospinal fluid (CSF) of a 78-year-old woman and a 65-year-old man. Both developed subacute severe cerebellar ataxia. Brain magnetic resonance imaging found no abnormality and no cerebellar atrophy. Both had CSF inflammation with mild pleiocytosis and a few oligoclonal bands. We identified a pulmonary adenocarcinoma, confirming the paraneoplastic neurological syndrome in both patients. They received immunomodulatory and cancer treatments without improvement of cerebellar ataxia, even though both were in remission of their cancer (for more than 10 years in one patient). Anti-TRIM9 and anti-TRIM67 Abs were specific to these two patients. All control serum and CSF samples tested were negative for anti-TRIM9 and 67. Anti-TRIM9 and anti-TRIM67 Abs appeared to be specific biomarkers of PCD and should be added to the panel of antigens tested when this is suspected.}, keywords = {}, pubstate = {published}, tppubtype = {article} } To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67, and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, 36 patients with lung adenocarcinoma and PNS, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases. We found Abs targeting TRIM9 and TRIM67 at high concentration in the serum and the cerebrospinal fluid (CSF) of a 78-year-old woman and a 65-year-old man. Both developed subacute severe cerebellar ataxia. Brain magnetic resonance imaging found no abnormality and no cerebellar atrophy. Both had CSF inflammation with mild pleiocytosis and a few oligoclonal bands. We identified a pulmonary adenocarcinoma, confirming the paraneoplastic neurological syndrome in both patients. They received immunomodulatory and cancer treatments without improvement of cerebellar ataxia, even though both were in remission of their cancer (for more than 10 years in one patient). Anti-TRIM9 and anti-TRIM67 Abs were specific to these two patients. All control serum and CSF samples tested were negative for anti-TRIM9 and 67. Anti-TRIM9 and anti-TRIM67 Abs appeared to be specific biomarkers of PCD and should be added to the panel of antigens tested when this is suspected. |
Wieczorek, Samuel; Giai Gianetto, Quentin ; Burger, Thomas Five simple yet essential steps to correctly estimate the rate of false differentially abundant proteins in mass spectrometry analyses Article de journal Journal of Proteomics, 207 , p. 103441, 2019, ISSN: 18743919. @article{wieczorek_five_2019, title = {Five simple yet essential steps to correctly estimate the rate of false differentially abundant proteins in mass spectrometry analyses}, author = {Samuel Wieczorek and Quentin {Giai Gianetto} and Thomas Burger}, url = {https://linkinghub.elsevier.com/retrieve/pii/S1874391919302131}, doi = {10.1016/j.jprot.2019.103441}, issn = {18743919}, year = {2019}, date = {2019-01-01}, journal = {Journal of Proteomics}, volume = {207}, pages = {103441}, abstract = {Results from mass spectrometry based quantitative proteomics analysis correspond to a subset of proteins which are considered differentially abundant relative to a control. Their selection is delicate and often requires some statistical expertise in addition to a refined knowledge of the experimental data. To facilitate the selection process, we have considered differential analysis as a five-step process, and here we present the practical aspects of the different steps. Prostar software is used throughout this article for illustration, but the general methodology is applicable with many other tools. By applying the approach detailed here, researchers who may be less familiar with statistical considerations can be more confident in the results they present.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Results from mass spectrometry based quantitative proteomics analysis correspond to a subset of proteins which are considered differentially abundant relative to a control. Their selection is delicate and often requires some statistical expertise in addition to a refined knowledge of the experimental data. To facilitate the selection process, we have considered differential analysis as a five-step process, and here we present the practical aspects of the different steps. Prostar software is used throughout this article for illustration, but the general methodology is applicable with many other tools. By applying the approach detailed here, researchers who may be less familiar with statistical considerations can be more confident in the results they present. |
Wei, Jiajie; Kishton, Rigel J; Angel, Matthew; Conn, Crystal S; Dalla-Venezia, Nicole; Marcel, Virginie; Vincent, Anne; Catez, Frédéric; Ferré, Sabrina; Ayadi, Lilia; Marchand, Virginie; Dersh, Devin; Gibbs, James S; Ivanov, Ivaylo P; Fridlyand, Nathan; Couté, Yohann; Diaz, Jean-Jacques; Qian, Shu-Bing; Staudt, Louis M; Restifo, Nicholas P; Yewdell, Jonathan W Ribosomal Proteins Regulate MHC Class I Peptide Generation for Immunosurveillance Article de journal Molecular Cell, 2019, ISSN: 1097-4164. @article{wei_ribosomal_2019, title = {Ribosomal Proteins Regulate MHC Class I Peptide Generation for Immunosurveillance}, author = {Jiajie Wei and Rigel J Kishton and Matthew Angel and Crystal S Conn and Nicole Dalla-Venezia and Virginie Marcel and Anne Vincent and Frédéric Catez and Sabrina Ferré and Lilia Ayadi and Virginie Marchand and Devin Dersh and James S Gibbs and Ivaylo P Ivanov and Nathan Fridlyand and Yohann Couté and Jean-Jacques Diaz and Shu-Bing Qian and Louis M Staudt and Nicholas P Restifo and Jonathan W Yewdell}, doi = {10.1016/j.molcel.2018.12.020}, issn = {1097-4164}, year = {2019}, date = {2019-01-01}, journal = {Molecular Cell}, abstract = {The MHC class I antigen presentation system enables T cell immunosurveillance of cancers and viruses. A substantial fraction of the immunopeptidome derives from rapidly degraded nascent polypeptides (DRiPs). By knocking down each of the 80 ribosomal proteins, we identified proteins that modulate peptide generation without altering source protein expression. We show that 60S ribosomal proteins L6 (RPL6) and RPL28, which are adjacent on the ribosome, play opposite roles in generating an influenza A virus-encoded peptide. Depleting RPL6 decreases ubiquitin-dependent peptide presentation, whereas depleting RPL28 increases ubiquitin-dependent and -independent peptide presentation. 40S ribosomal protein S28 (RPS28) knockdown increases total peptide supply in uninfected cells by increasing DRiP synthesis from non-canonical translation of "untranslated" regions and non-AUG start codons and sensitizes tumor cells for T cell targeting. Our findings raise the possibility of modulating immunosurveillance by pharmaceutical targeting ribosomes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The MHC class I antigen presentation system enables T cell immunosurveillance of cancers and viruses. A substantial fraction of the immunopeptidome derives from rapidly degraded nascent polypeptides (DRiPs). By knocking down each of the 80 ribosomal proteins, we identified proteins that modulate peptide generation without altering source protein expression. We show that 60S ribosomal proteins L6 (RPL6) and RPL28, which are adjacent on the ribosome, play opposite roles in generating an influenza A virus-encoded peptide. Depleting RPL6 decreases ubiquitin-dependent peptide presentation, whereas depleting RPL28 increases ubiquitin-dependent and -independent peptide presentation. 40S ribosomal protein S28 (RPS28) knockdown increases total peptide supply in uninfected cells by increasing DRiP synthesis from non-canonical translation of "untranslated" regions and non-AUG start codons and sensitizes tumor cells for T cell targeting. Our findings raise the possibility of modulating immunosurveillance by pharmaceutical targeting ribosomes. |
Kraut, Alexandra; Louwagie, Mathilde; Bruley, Christophe; Masselon, Christophe; Couté, Yohann; Brun, Virginie; Hesse, Anne-Marie Protein Biomarker Discovery in Non-depleted Serum by Spectral Library-Based Data-Independent Acquisition Mass Spectrometry Article de journal Methods in Molecular Biology (Clifton, N.J.), 1959 , p. 129–150, 2019, ISSN: 1940-6029. @article{kraut_protein_2019, title = {Protein Biomarker Discovery in Non-depleted Serum by Spectral Library-Based Data-Independent Acquisition Mass Spectrometry}, author = {Alexandra Kraut and Mathilde Louwagie and Christophe Bruley and Christophe Masselon and Yohann Couté and Virginie Brun and Anne-Marie Hesse}, doi = {10.1007/978-1-4939-9164-8_9}, issn = {1940-6029}, year = {2019}, date = {2019-01-01}, journal = {Methods in Molecular Biology (Clifton, N.J.)}, volume = {1959}, pages = {129--150}, abstract = {In discovery proteomics experiments, tandem mass spectrometry and data-dependent acquisition (DDA) are classically used to identify and quantify peptides and proteins through database searching. This strategy suffers from known limitations such as under-sampling and lack of reproducibility of precursor ion selection in complex proteomics samples, leading to somewhat inconsistent analytical results across large datasets. Data-independent acquisition (DIA) based on fragmentation of all the precursors detected in predetermined isolation windows can potentially overcome this limitation. DIA promises reproducible peptide and protein quantification with deeper proteome coverage and fewer missing values than DDA strategies. This approach is particularly attractive in the field of clinical biomarker discovery, where large numbers of samples must be analyzed. Here, we describe a DIA workflow for non-depleted serum analysis including a straightforward approach through which to construct a dedicated spectral library, and indications on how to optimize chromatographic and mass spectrometry analytical methods to produce high-quality DIA data and results.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In discovery proteomics experiments, tandem mass spectrometry and data-dependent acquisition (DDA) are classically used to identify and quantify peptides and proteins through database searching. This strategy suffers from known limitations such as under-sampling and lack of reproducibility of precursor ion selection in complex proteomics samples, leading to somewhat inconsistent analytical results across large datasets. Data-independent acquisition (DIA) based on fragmentation of all the precursors detected in predetermined isolation windows can potentially overcome this limitation. DIA promises reproducible peptide and protein quantification with deeper proteome coverage and fewer missing values than DDA strategies. This approach is particularly attractive in the field of clinical biomarker discovery, where large numbers of samples must be analyzed. Here, we describe a DIA workflow for non-depleted serum analysis including a straightforward approach through which to construct a dedicated spectral library, and indications on how to optimize chromatographic and mass spectrometry analytical methods to produce high-quality DIA data and results. |
Steingruber, Mirjam; Keller, Lena; Socher, Eileen; Ferre, Sabrina; Hesse, Anne-Marie; Couté, Yohann; Hahn, Friedrich; Büscher, Nicole; Plachter, Bodo; Sticht, Heinrich; Marschall, Manfred Cyclins B1, T1, and H differ in their molecular mode of interaction with cytomegalovirus protein kinase pUL97 Article de journal The Journal of Biological Chemistry, 294 (15), p. 6188–6203, 2019, ISSN: 1083-351X. @article{steingruber_cyclins_2019, title = {Cyclins B1, T1, and H differ in their molecular mode of interaction with cytomegalovirus protein kinase pUL97}, author = {Mirjam Steingruber and Lena Keller and Eileen Socher and Sabrina Ferre and Anne-Marie Hesse and Yohann Couté and Friedrich Hahn and Nicole Büscher and Bodo Plachter and Heinrich Sticht and Manfred Marschall}, doi = {10.1074/jbc.RA118.007049}, issn = {1083-351X}, year = {2019}, date = {2019-01-01}, journal = {The Journal of Biological Chemistry}, volume = {294}, number = {15}, pages = {6188--6203}, abstract = {Human cytomegalovirus (HCMV) is a common $beta$-herpesvirus causing life-long latent infections. HCMV replication interferes with cell cycle regulation in host cells because the HCMV-encoded cyclin-dependent kinase (CDK) ortholog pUL97 extensively phosphorylates the checkpoint regulator retinoblastoma protein. pUL97 also interacts with cyclins B1, T1, and H, and recent findings have strongly suggested that these interactions influence pUL97 substrate recognition. Interestingly, here we detected profound mechanistic differences among these pUL97-cyclin interactions. Our study revealed the following. (i) pUL97 interacts with cyclins B1 and H in a manner dependent on pUL97 activity and HCMV-specific cyclin modulation, respectively. (ii) The phosphorylated state of both proteins is an important determinant of the pUL97-cyclin B1 interaction. (iii) Activated phospho-Thr-315 cyclin H is up-regulated during HCMV replication. (iv) Thr-315 phosphorylation is independent of intracellular pUL97 or CDK7 activity. (v) pUL97-mediated in vitro phosphorylation is detectable for cyclin B1 but not H. (vi) Mutual transphosphorylation between pUL97 and CDK7 is not detectable, and an MS-based phosphosite analysis indicated that pUL97 might unexpectedly not be phosphorylated in its T-loop. (vii) The binary complexes pUL97-cyclin H and CDK7-cyclin H as well as the ternary complex pUL97-cyclin-H-CDK7 are detectable in an assembly-based CoIP approach. (viii) pUL97 self-interaction can be bridged by the transcriptional cyclins T1 or H but not by the classical cell cycle-regulating B1 cyclin. Combined, our findings unravel a number of cyclin type-specific differences in pUL97 interactions and suggest a multifaceted regulatory impact of cyclins on HCMV replication.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Human cytomegalovirus (HCMV) is a common $beta$-herpesvirus causing life-long latent infections. HCMV replication interferes with cell cycle regulation in host cells because the HCMV-encoded cyclin-dependent kinase (CDK) ortholog pUL97 extensively phosphorylates the checkpoint regulator retinoblastoma protein. pUL97 also interacts with cyclins B1, T1, and H, and recent findings have strongly suggested that these interactions influence pUL97 substrate recognition. Interestingly, here we detected profound mechanistic differences among these pUL97-cyclin interactions. Our study revealed the following. (i) pUL97 interacts with cyclins B1 and H in a manner dependent on pUL97 activity and HCMV-specific cyclin modulation, respectively. (ii) The phosphorylated state of both proteins is an important determinant of the pUL97-cyclin B1 interaction. (iii) Activated phospho-Thr-315 cyclin H is up-regulated during HCMV replication. (iv) Thr-315 phosphorylation is independent of intracellular pUL97 or CDK7 activity. (v) pUL97-mediated in vitro phosphorylation is detectable for cyclin B1 but not H. (vi) Mutual transphosphorylation between pUL97 and CDK7 is not detectable, and an MS-based phosphosite analysis indicated that pUL97 might unexpectedly not be phosphorylated in its T-loop. (vii) The binary complexes pUL97-cyclin H and CDK7-cyclin H as well as the ternary complex pUL97-cyclin-H-CDK7 are detectable in an assembly-based CoIP approach. (viii) pUL97 self-interaction can be bridged by the transcriptional cyclins T1 or H but not by the classical cell cycle-regulating B1 cyclin. Combined, our findings unravel a number of cyclin type-specific differences in pUL97 interactions and suggest a multifaceted regulatory impact of cyclins on HCMV replication. |
Siebert, Claire; Lindgren, Helena; Ferré, Sabrina; Villers, Corinne; Boisset, Sandrine; Perard, Julien; Sjöstedt, Anders; Maurin, Max; Brochier-Armanet, Céline; Couté, Yohann; Renesto, Patricia Francisella tularensis: FupA mutation contributes to fluoroquinolone resistance by increasing vesicle secretion and biofilm formation Article de journal Emerging Microbes & Infections, 8 (1), p. 808–822, 2019, ISSN: 2222-1751. @article{siebert_francisella_2019, title = {Francisella tularensis: FupA mutation contributes to fluoroquinolone resistance by increasing vesicle secretion and biofilm formation}, author = {Claire Siebert and Helena Lindgren and Sabrina Ferré and Corinne Villers and Sandrine Boisset and Julien Perard and Anders Sjöstedt and Max Maurin and Céline Brochier-Armanet and Yohann Couté and Patricia Renesto}, doi = {10.1080/22221751.2019.1615848}, issn = {2222-1751}, year = {2019}, date = {2019-01-01}, journal = {Emerging Microbes & Infections}, volume = {8}, number = {1}, pages = {808--822}, abstract = {Francisella tularensis is the causative agent in tularemia for which the high prevalence of treatment failure and relapse is a major concern. Directed-evolution experiments revealed that acquisition of fluoroquinolone (FQ) resistance was linked to factors in addition to mutations in DNA gyrase. Here, using F. tularensis live vaccine strain (LVS) as a model, we demonstrated that FupA/B (Fer-Utilization Protein) expression is linked to FQ susceptibility, and that the virulent strain F. tularensis subsp. tularensis SCHU S4 deleted for the homologous FupA protein exhibited even higher FQ resistance. In addition to an increased FQ minimal inhibitory concentration, LVS$Delta$fupA/B displayed tolerance toward bactericidal compounds including ciprofloxacin and gentamicin. Interestingly, the FupA/B deletion was found to promote increased secretion of outer membrane vesicles (OMVs). Mass spectrometry-based quantitative proteomic characterization of vesicles from LVS and LVS∆fupA/B identified 801 proteins, including a subset of 23 proteins exhibiting differential abundance between both strains which may therefore contribute to the reduced antibiotic susceptibility of the FupA/B-deleted strain. We also demonstrated that OMVs are key structural elements of LVS$Delta$fupA/B biofilms providing protection against FQ. These results provide a new basis for understanding and tackling antibiotic resistance and/or persistence of Francisella and other pathogenic members of the Thiotrichales class.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Francisella tularensis is the causative agent in tularemia for which the high prevalence of treatment failure and relapse is a major concern. Directed-evolution experiments revealed that acquisition of fluoroquinolone (FQ) resistance was linked to factors in addition to mutations in DNA gyrase. Here, using F. tularensis live vaccine strain (LVS) as a model, we demonstrated that FupA/B (Fer-Utilization Protein) expression is linked to FQ susceptibility, and that the virulent strain F. tularensis subsp. tularensis SCHU S4 deleted for the homologous FupA protein exhibited even higher FQ resistance. In addition to an increased FQ minimal inhibitory concentration, LVS$Delta$fupA/B displayed tolerance toward bactericidal compounds including ciprofloxacin and gentamicin. Interestingly, the FupA/B deletion was found to promote increased secretion of outer membrane vesicles (OMVs). Mass spectrometry-based quantitative proteomic characterization of vesicles from LVS and LVS∆fupA/B identified 801 proteins, including a subset of 23 proteins exhibiting differential abundance between both strains which may therefore contribute to the reduced antibiotic susceptibility of the FupA/B-deleted strain. We also demonstrated that OMVs are key structural elements of LVS$Delta$fupA/B biofilms providing protection against FQ. These results provide a new basis for understanding and tackling antibiotic resistance and/or persistence of Francisella and other pathogenic members of the Thiotrichales class. |
Lupette, Josselin; Jaussaud, Antoine; Seddiki, Khawla; Morabito, Christian; è, Sabine Brugi; Schaller, Hubert; Kuntz, Marcel; Putaux, Jean-Luc; Jouneau, Pierre-Henri; Rébeillé, Fabrice; Falconet, Denis; Couté, Yohann; Jouhet, Juliette; Tardif, Marianne; Salvaing, Juliette; Maréchal, Eric The architecture of lipid droplets in the diatom Phaeodactylum tricornutum Article de journal Algal Research, 38 , p. 101415, 2019, ISSN: 2211-9264. @article{lupette_architecture_2019, title = {The architecture of lipid droplets in the diatom Phaeodactylum tricornutum}, author = {Josselin Lupette and Antoine Jaussaud and Khawla Seddiki and Christian Morabito and Sabine Brugi{è}re and Hubert Schaller and Marcel Kuntz and Jean-Luc Putaux and Pierre-Henri Jouneau and Fabrice Rébeillé and Denis Falconet and Yohann Couté and Juliette Jouhet and Marianne Tardif and Juliette Salvaing and Eric Maréchal}, url = {http://www.sciencedirect.com/science/article/pii/S2211926418309160}, doi = {10.1016/j.algal.2019.101415}, issn = {2211-9264}, year = {2019}, date = {2019-01-01}, journal = {Algal Research}, volume = {38}, pages = {101415}, abstract = {Diatoms are a major phylum of phytoplankton biodiversity and a resource considered for biotechnological developments, as feedstock for biofuels and applications ranging from food, human health or green chemistry. They contain a secondary plastid limited by four membranes, the outermost one being connected with the endoplasmic reticulum (ER). Upon nitrogen stress, diatoms reallocate carbon to triacylglycerol storage inside lipid droplets (LDs). The comprehensive glycerolipid and sterol composition and the architecture of diatom LDs are unknown. In Phaeodactylum tricornutum, LDs are in contact with plastid, mitochondria and uncharacterized endomembranes. We purified LDs from nitrogen-starved P. tricornutum cells to high purity level (99 mol% triacylglycerol of total glycerolipids). We used the Stramenopile Lipid Droplet Protein (StLDP) as a previously validated marker for the identity of P. tricornutum LD. Amphipathic lipids surrounding LDs consist of a betaine lipid, diacylglycerylhydroxymethyltrimethyl‑$beta$‑alanine (0.4 mol%); sulfoquinovosyldiacylglycerol (0.35 mol%); phosphatidylcholine (0.15 mol%) and one sterol, brassicasterol. By contrast with whole cell extracts, the betaine lipid from LDs only contains eicosapentaenoic acid paired with palmitoleic or palmitolenic acids. This polar lipid composition suggests a budding of LDs from the cytosolic leaflet of the plastid outermost membrane. LD pigments reveal a specific accumulation of $beta$‑carotene. The LD proteome obtained from three independent biological replicates, based on stringent filtering of extracted data, and following subtraction of proteins downregulated by nitrogen starvation, highlights a core proteome of 86 proteins, including StLDP. LD-associated proteins suggest connections with vesicular trafficking (coatomer, clathrin), cytoskeleton, plastid and mitochondria. Unsuspected LD-associated function includes protein synthesis (ribosomes), folding (chaperones), posttranslational modifications and quality control (ubiquitination and ERAD pathway), possibly preparing translation of specific mRNAs. The detection of histone proteins, as previously demonstrated in drosophila embryo LDs, also suggests the storage of nucleosome components, preparing cell division and chromatin packaging, when cells are not stressed anymore.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Diatoms are a major phylum of phytoplankton biodiversity and a resource considered for biotechnological developments, as feedstock for biofuels and applications ranging from food, human health or green chemistry. They contain a secondary plastid limited by four membranes, the outermost one being connected with the endoplasmic reticulum (ER). Upon nitrogen stress, diatoms reallocate carbon to triacylglycerol storage inside lipid droplets (LDs). The comprehensive glycerolipid and sterol composition and the architecture of diatom LDs are unknown. In Phaeodactylum tricornutum, LDs are in contact with plastid, mitochondria and uncharacterized endomembranes. We purified LDs from nitrogen-starved P. tricornutum cells to high purity level (99 mol% triacylglycerol of total glycerolipids). We used the Stramenopile Lipid Droplet Protein (StLDP) as a previously validated marker for the identity of P. tricornutum LD. Amphipathic lipids surrounding LDs consist of a betaine lipid, diacylglycerylhydroxymethyltrimethyl‑$beta$‑alanine (0.4 mol%); sulfoquinovosyldiacylglycerol (0.35 mol%); phosphatidylcholine (0.15 mol%) and one sterol, brassicasterol. By contrast with whole cell extracts, the betaine lipid from LDs only contains eicosapentaenoic acid paired with palmitoleic or palmitolenic acids. This polar lipid composition suggests a budding of LDs from the cytosolic leaflet of the plastid outermost membrane. LD pigments reveal a specific accumulation of $beta$‑carotene. The LD proteome obtained from three independent biological replicates, based on stringent filtering of extracted data, and following subtraction of proteins downregulated by nitrogen starvation, highlights a core proteome of 86 proteins, including StLDP. LD-associated proteins suggest connections with vesicular trafficking (coatomer, clathrin), cytoskeleton, plastid and mitochondria. Unsuspected LD-associated function includes protein synthesis (ribosomes), folding (chaperones), posttranslational modifications and quality control (ubiquitination and ERAD pathway), possibly preparing translation of specific mRNAs. The detection of histone proteins, as previously demonstrated in drosophila embryo LDs, also suggests the storage of nucleosome components, preparing cell division and chromatin packaging, when cells are not stressed anymore. |
Bouchnak, Imen; è, Sabine Brugi; Moyet, Lucas; Le Gall, Sophie ; Salvi, Daniel; Kuntz, Marcel; Tardif, Marianne; Rolland, Norbert Unraveling Hidden Components of the Chloroplast Envelope Proteome: Opportunities and Limits of Better MS Sensitivity Article de journal Molecular & cellular proteomics: MCP, 18 (7), p. 1285–1306, 2019, ISSN: 1535-9484. @article{bouchnak_unraveling_2019, title = {Unraveling Hidden Components of the Chloroplast Envelope Proteome: Opportunities and Limits of Better MS Sensitivity}, author = {Imen Bouchnak and Sabine Brugi{è}re and Lucas Moyet and Sophie {Le Gall} and Daniel Salvi and Marcel Kuntz and Marianne Tardif and Norbert Rolland}, doi = {10.1074/mcp.RA118.000988}, issn = {1535-9484}, year = {2019}, date = {2019-01-01}, journal = {Molecular & cellular proteomics: MCP}, volume = {18}, number = {7}, pages = {1285--1306}, abstract = {The chloroplast is a major plant cell organelle that fulfills essential metabolic and biosynthetic functions. Located at the interface between the chloroplast and other cell compartments, the chloroplast envelope system is a strategic barrier controlling the exchange of ions, metabolites and proteins, thus regulating essential metabolic functions (synthesis of hormones precursors, amino acids, pigments, sugars, vitamins, lipids, nucleotides etc.) of the plant cell. However, unraveling the contents of the chloroplast envelope proteome remains a difficult challenge; many proteins constituting this functional double membrane system remain to be identified. Indeed, the envelope contains only 1% of the chloroplast proteins (i.e. 0.4% of the whole cell proteome). In other words, most envelope proteins are so rare at the cell, chloroplast, or even envelope level, that they remained undetectable using targeted MS studies. Cross-contamination of chloroplast subcompartments by each other and by other cell compartments during cell fractionation, impedes accurate localization of many envelope proteins. The aim of the present study was to take advantage of technologically improved MS sensitivity to better define the proteome of the chloroplast envelope (differentiate genuine envelope proteins from contaminants). This MS-based analysis relied on an enrichment factor that was calculated for each protein identified in purified envelope fractions as compared with the value obtained for the same protein in crude cell extracts. Using this approach, a total of 1269 proteins were detected in purified envelope fractions, of which, 462 could be assigned an envelope localization by combining MS-based spectral count analyses with manual annotation using data from the literature and prediction tools. Many of such proteins being previously unknown envelope components, these data constitute a new resource of significant value to the broader plant science community aiming to define principles and molecular mechanisms controlling fundamental aspects of plastid biogenesis and functions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The chloroplast is a major plant cell organelle that fulfills essential metabolic and biosynthetic functions. Located at the interface between the chloroplast and other cell compartments, the chloroplast envelope system is a strategic barrier controlling the exchange of ions, metabolites and proteins, thus regulating essential metabolic functions (synthesis of hormones precursors, amino acids, pigments, sugars, vitamins, lipids, nucleotides etc.) of the plant cell. However, unraveling the contents of the chloroplast envelope proteome remains a difficult challenge; many proteins constituting this functional double membrane system remain to be identified. Indeed, the envelope contains only 1% of the chloroplast proteins (i.e. 0.4% of the whole cell proteome). In other words, most envelope proteins are so rare at the cell, chloroplast, or even envelope level, that they remained undetectable using targeted MS studies. Cross-contamination of chloroplast subcompartments by each other and by other cell compartments during cell fractionation, impedes accurate localization of many envelope proteins. The aim of the present study was to take advantage of technologically improved MS sensitivity to better define the proteome of the chloroplast envelope (differentiate genuine envelope proteins from contaminants). This MS-based analysis relied on an enrichment factor that was calculated for each protein identified in purified envelope fractions as compared with the value obtained for the same protein in crude cell extracts. Using this approach, a total of 1269 proteins were detected in purified envelope fractions, of which, 462 could be assigned an envelope localization by combining MS-based spectral count analyses with manual annotation using data from the literature and prediction tools. Many of such proteins being previously unknown envelope components, these data constitute a new resource of significant value to the broader plant science community aiming to define principles and molecular mechanisms controlling fundamental aspects of plastid biogenesis and functions. |
Moulin, M; Mossou, E; Signor, L; Kieffer-Jaquinod, S; Kwaambwa, H M; Nermark, F; Gutfreund, P; Mitchell, E P; Haertlein, M; Forsyth, V T; Rennie, A R Towards a molecular understanding of the water purification properties of Moringa seed proteins Article de journal Journal of Colloid and Interface Science, 554 , p. 296–304, 2019, ISSN: 1095-7103. @article{moulin_towards_2019, title = {Towards a molecular understanding of the water purification properties of Moringa seed proteins}, author = {M Moulin and E Mossou and L Signor and S Kieffer-Jaquinod and H M Kwaambwa and F Nermark and P Gutfreund and E P Mitchell and M Haertlein and V T Forsyth and A R Rennie}, doi = {10.1016/j.jcis.2019.06.071}, issn = {1095-7103}, year = {2019}, date = {2019-01-01}, journal = {Journal of Colloid and Interface Science}, volume = {554}, pages = {296--304}, abstract = {Seed extracts from Moringa oleifera are of wide interest for use in water purification where they can play an important role in flocculation; they also have potential as anti-microbial agents. Previous work has focused on the crude protein extract. Here we describe the detailed biophysical characterization of individual proteins from these seeds. The results provide new insights relating to the active compounds involved. One fraction, designated Mo-CBP3, has been characterized at a molecular level using a range of biochemical and biophysical techniques including liquid chromatography, X-ray diffraction, mass spectrometry, and neutron reflection. The interfacial behavior is of particular interest in considering water purification applications and interactions with both charged (e.g. silica) and uncharged (alumina) surfaces were studied. The reflection studies show that, in marked contrast to the crude extract, only a single layer of the purified Mo-CBP3 binds to a silica interface and that there is no binding to an alumina interface. These observations are consistent with the crystallographic structure of Mo-CBP3-4, which is one of the main isoforms of the Mo-CBP3 fraction. The results are put in context of previous studies of the properties of the crude extract. This work shows possible routes to development of separation processes that would be based on the specific properties of individual proteins.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Seed extracts from Moringa oleifera are of wide interest for use in water purification where they can play an important role in flocculation; they also have potential as anti-microbial agents. Previous work has focused on the crude protein extract. Here we describe the detailed biophysical characterization of individual proteins from these seeds. The results provide new insights relating to the active compounds involved. One fraction, designated Mo-CBP3, has been characterized at a molecular level using a range of biochemical and biophysical techniques including liquid chromatography, X-ray diffraction, mass spectrometry, and neutron reflection. The interfacial behavior is of particular interest in considering water purification applications and interactions with both charged (e.g. silica) and uncharged (alumina) surfaces were studied. The reflection studies show that, in marked contrast to the crude extract, only a single layer of the purified Mo-CBP3 binds to a silica interface and that there is no binding to an alumina interface. These observations are consistent with the crystallographic structure of Mo-CBP3-4, which is one of the main isoforms of the Mo-CBP3 fraction. The results are put in context of previous studies of the properties of the crude extract. This work shows possible routes to development of separation processes that would be based on the specific properties of individual proteins. |
Hajj Chehade, Mahmoud ; Pelosi, Ludovic; Fyfe, Cameron David; Loiseau, Laurent; è, Béreng; è, Sabine Brugi; Kazemzadeh, Katayoun; Vo, Chau-Duy-Tam; Ciccone, Lidia; Aussel, Laurent; Couté, Yohann; Fontecave, Marc; Barras, Frédéric; Lombard, Murielle; Pierrel, Fabien A Soluble Metabolon Synthesizes the Isoprenoid Lipid Ubiquinone Article de journal Cell Chemical Biology, 26 (4), p. 482––492.e7, 2019, ISSN: 2451-9448. @article{hajj_chehade_soluble_2019, title = {A Soluble Metabolon Synthesizes the Isoprenoid Lipid Ubiquinone}, author = {Mahmoud {Hajj Chehade} and Ludovic Pelosi and Cameron David Fyfe and Laurent Loiseau and Béreng{è}re Rascalou and Sabine Brugi{è}re and Katayoun Kazemzadeh and Chau-Duy-Tam Vo and Lidia Ciccone and Laurent Aussel and Yohann Couté and Marc Fontecave and Frédéric Barras and Murielle Lombard and Fabien Pierrel}, doi = {10.1016/j.chembiol.2018.12.001}, issn = {2451-9448}, year = {2019}, date = {2019-01-01}, journal = {Cell Chemical Biology}, volume = {26}, number = {4}, pages = {482----492.e7}, abstract = {Ubiquinone (UQ) is a polyprenylated lipid that is conserved from bacteria to humans and is crucial to cellular respiration. How the cell orchestrates the efficient synthesis of UQ, which involves the modification of extremely hydrophobic substrates by multiple sequential enzymes, remains an unresolved issue. Here, we demonstrate that seven Ubi proteins form the Ubi complex, a stable metabolon that catalyzes the last six reactions of the UQ biosynthetic pathway in Escherichia coli. The SCP2 domain of UbiJ forms an extended hydrophobic cavity that binds UQ intermediates inside the 1-MDa Ubi complex. We purify the Ubi complex from cytoplasmic extracts and demonstrate that UQ biosynthesis occurs in this fraction, challenging the current thinking of a membrane-associated biosynthetic process. Collectively, our results document a rare case of stable metabolon and highlight how the supramolecular organization of soluble enzymes allows the modification of hydrophobic substrates in a hydrophilic environment.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Ubiquinone (UQ) is a polyprenylated lipid that is conserved from bacteria to humans and is crucial to cellular respiration. How the cell orchestrates the efficient synthesis of UQ, which involves the modification of extremely hydrophobic substrates by multiple sequential enzymes, remains an unresolved issue. Here, we demonstrate that seven Ubi proteins form the Ubi complex, a stable metabolon that catalyzes the last six reactions of the UQ biosynthetic pathway in Escherichia coli. The SCP2 domain of UbiJ forms an extended hydrophobic cavity that binds UQ intermediates inside the 1-MDa Ubi complex. We purify the Ubi complex from cytoplasmic extracts and demonstrate that UQ biosynthesis occurs in this fraction, challenging the current thinking of a membrane-associated biosynthetic process. Collectively, our results document a rare case of stable metabolon and highlight how the supramolecular organization of soluble enzymes allows the modification of hydrophobic substrates in a hydrophilic environment. |
Sentausa, Erwin; Basso, Pauline; Berry, Alice; Adrait, Annie; Bellement, Gwendoline; Couté, Yohann; Lory, Stephen; Elsen, Sylvie; Attrée, Ina Insertion sequences drive the emergence of a highly adapted human pathogen Article de journal Microbial Genomics, 2019, ISSN: 2057-5858. @article{sentausa_insertion_2019, title = {Insertion sequences drive the emergence of a highly adapted human pathogen}, author = {Erwin Sentausa and Pauline Basso and Alice Berry and Annie Adrait and Gwendoline Bellement and Yohann Couté and Stephen Lory and Sylvie Elsen and Ina Attrée}, doi = {10.1099/mgen.0.000265}, issn = {2057-5858}, year = {2019}, date = {2019-01-01}, journal = {Microbial Genomics}, abstract = {Pseudomonas aeruginosa is a highly adaptive opportunistic pathogen that can have serious health consequences in patients with lung disorders. Taxonomic outliers of P. aeruginosa of environmental origin have recently emerged as infectious for humans. Here, we present the first genome-wide analysis of an isolate that caused fatal haemorrhagic pneumonia. In two clones, CLJ1 and CLJ3, sequentially recovered from a patient with chronic pulmonary disease, insertion of a mobile genetic element into the P. aeruginosa chromosome affected major virulence-associated phenotypes and led to increased resistance to the antibiotics used to combat the infection. Comparative genome, proteome and transcriptome analyses revealed that this ISL3-family insertion sequence disrupted the genes for flagellar components, type IV pili, O-specific antigens, translesion polymerase and enzymes producing hydrogen cyanide. Seven-fold more insertions were detected in the later isolate, CLJ3, than in CLJ1, some of which modified strain susceptibility to antibiotics by disrupting the genes for the outer-membrane porin OprD and the regulator of $beta$-lactamase expression AmpD. In the Galleria mellonella larvae model, the two strains displayed different levels of virulence, with CLJ1 being highly pathogenic. This study revealed insertion sequences to be major players in enhancing the pathogenic potential of a P. aeruginosa taxonomic outlier by modulating both its virulence and its resistance to antimicrobials, and explains how this bacterium adapts from the environment to a human host.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Pseudomonas aeruginosa is a highly adaptive opportunistic pathogen that can have serious health consequences in patients with lung disorders. Taxonomic outliers of P. aeruginosa of environmental origin have recently emerged as infectious for humans. Here, we present the first genome-wide analysis of an isolate that caused fatal haemorrhagic pneumonia. In two clones, CLJ1 and CLJ3, sequentially recovered from a patient with chronic pulmonary disease, insertion of a mobile genetic element into the P. aeruginosa chromosome affected major virulence-associated phenotypes and led to increased resistance to the antibiotics used to combat the infection. Comparative genome, proteome and transcriptome analyses revealed that this ISL3-family insertion sequence disrupted the genes for flagellar components, type IV pili, O-specific antigens, translesion polymerase and enzymes producing hydrogen cyanide. Seven-fold more insertions were detected in the later isolate, CLJ3, than in CLJ1, some of which modified strain susceptibility to antibiotics by disrupting the genes for the outer-membrane porin OprD and the regulator of $beta$-lactamase expression AmpD. In the Galleria mellonella larvae model, the two strains displayed different levels of virulence, with CLJ1 being highly pathogenic. This study revealed insertion sequences to be major players in enhancing the pathogenic potential of a P. aeruginosa taxonomic outlier by modulating both its virulence and its resistance to antimicrobials, and explains how this bacterium adapts from the environment to a human host. |
Braun, Laurence; Brenier-Pinchart, Marie-Pierre; Hammoudi, Pierre-Mehdi; Cannella, Dominique; Kieffer-Jaquinod, Sylvie; Vollaire, Julien; Josserand, Véronique; Touquet, Bastien; Couté, Yohann; Tardieux, Isabelle; Bougdour, Alexandre; Hakimi, Mohamed-Ali The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-$kappa$B signalling via EZH2 Article de journal Nature Microbiology, 4 (7), p. 1208–1220, 2019, ISSN: 2058-5276. @article{braun_toxoplasma_2019, title = {The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-$kappa$B signalling via EZH2}, author = {Laurence Braun and Marie-Pierre Brenier-Pinchart and Pierre-Mehdi Hammoudi and Dominique Cannella and Sylvie Kieffer-Jaquinod and Julien Vollaire and Véronique Josserand and Bastien Touquet and Yohann Couté and Isabelle Tardieux and Alexandre Bougdour and Mohamed-Ali Hakimi}, doi = {10.1038/s41564-019-0431-8}, issn = {2058-5276}, year = {2019}, date = {2019-01-01}, journal = {Nature Microbiology}, volume = {4}, number = {7}, pages = {1208--1220}, abstract = {The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which starts with a small subset of parasites that escape host immune killing and colonize the so-called immune privileged tissues where they differentiate into a low replicating stage, is driven by the interleukin 12 (IL-12)-interferon-$gamma$ (IFN-$gamma$) axis. Recent characterization of a family of Toxoplasma effectors that are delivered into the host cell, in which they rewire the host cell gene expression, has allowed the identification of regulators of the IL-12-IFN-$gamma$ axis, including repressors. We now report on the dense granule-resident effector, called TEEGR (Toxoplasma E2F4-associated EZH2-inducing gene regulator) that counteracts the nuclear factor-$kappa$B (NF-$kappa$B) signalling pathway. Once exported into the host cell, TEEGR ends up in the nucleus where it not only complexes with the E2F3 and E2F4 host transcription factors to induce gene expression, but also promotes shaping of a non-permissive chromatin through its capacity to switch on EZH2. Remarkably, EZH2 fosters the epigenetic silencing of a subset of NF-$kappa$B-regulated cytokines, thereby strongly contributing to the host immune equilibrium that influences the host immune response and promotes parasite persistence in mice.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which starts with a small subset of parasites that escape host immune killing and colonize the so-called immune privileged tissues where they differentiate into a low replicating stage, is driven by the interleukin 12 (IL-12)-interferon-$gamma$ (IFN-$gamma$) axis. Recent characterization of a family of Toxoplasma effectors that are delivered into the host cell, in which they rewire the host cell gene expression, has allowed the identification of regulators of the IL-12-IFN-$gamma$ axis, including repressors. We now report on the dense granule-resident effector, called TEEGR (Toxoplasma E2F4-associated EZH2-inducing gene regulator) that counteracts the nuclear factor-$kappa$B (NF-$kappa$B) signalling pathway. Once exported into the host cell, TEEGR ends up in the nucleus where it not only complexes with the E2F3 and E2F4 host transcription factors to induce gene expression, but also promotes shaping of a non-permissive chromatin through its capacity to switch on EZH2. Remarkably, EZH2 fosters the epigenetic silencing of a subset of NF-$kappa$B-regulated cytokines, thereby strongly contributing to the host immune equilibrium that influences the host immune response and promotes parasite persistence in mice. |
Darrieutort-Laffite, Christelle; Arnolfo, Paul; Garraud, Thomas; Adrait, Annie; Couté, Yohann; Louarn, Guy; Trichet, Valérie; Layrolle, Pierre; Le Goff, Benoit ; Blanchard, Frédéric Rotator Cuff Tenocytes Differentiate into Hypertrophic Chondrocyte-Like Cells to Produce Calcium Deposits in an Alkaline Phosphatase-Dependent Manner Article de journal Journal of Clinical Medicine, 8 (10), 2019, ISSN: 2077-0383. @article{darrieutort-laffite_rotator_2019, title = {Rotator Cuff Tenocytes Differentiate into Hypertrophic Chondrocyte-Like Cells to Produce Calcium Deposits in an Alkaline Phosphatase-Dependent Manner}, author = {Christelle Darrieutort-Laffite and Paul Arnolfo and Thomas Garraud and Annie Adrait and Yohann Couté and Guy Louarn and Valérie Trichet and Pierre Layrolle and Benoit {Le Goff} and Frédéric Blanchard}, doi = {10.3390/jcm8101544}, issn = {2077-0383}, year = {2019}, date = {2019-01-01}, journal = {Journal of Clinical Medicine}, volume = {8}, number = {10}, abstract = {Calcific tendonitis is a frequent cause of chronic shoulder pain. Its cause is currently poorly known. The objectives of this study were to better characterize the cells and mechanisms involved in depositing apatite crystals in human tendons. Histologic sections of cadaveric calcified tendons were analyzed, and human calcific deposits from patients undergoing lavage of their calcification were obtained to perform infrared spectroscopy and mass spectrometry-based proteomic characterizations. In vitro, the mineralization ability of human rotator cuff cells from osteoarthritis donors was assessed by alizarin red or Von Kossa staining. Calcifications were amorphous areas surrounded by a fibrocartilaginous metaplasia containing hypertrophic chondrocyte-like cells that expressed tissue non-specific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which are two key enzymes of the mineralization process. Calcific deposits were composed of apatite crystals associated with proteins involved in bone and cartilage development and endochondral bone growth. In vitro, tenocyte-like cells extracted from the rotator cuff were able to mineralize in osteogenic cultures, and expressed TNAP, type X COLLAGEN, and MMP13, which are hypertrophic chondrocytes markers. The use of a TNAP inhibitor significantly prevented mineral deposits. We provide evidence that tenocytes have a propensity to differentiate into hypertrophic chondrocyte-like cells to produce TNAP-dependent calcium deposits. We believe that these results may pave the way to identifying regulating factors that might represent valuable targets in calcific tendonitis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Calcific tendonitis is a frequent cause of chronic shoulder pain. Its cause is currently poorly known. The objectives of this study were to better characterize the cells and mechanisms involved in depositing apatite crystals in human tendons. Histologic sections of cadaveric calcified tendons were analyzed, and human calcific deposits from patients undergoing lavage of their calcification were obtained to perform infrared spectroscopy and mass spectrometry-based proteomic characterizations. In vitro, the mineralization ability of human rotator cuff cells from osteoarthritis donors was assessed by alizarin red or Von Kossa staining. Calcifications were amorphous areas surrounded by a fibrocartilaginous metaplasia containing hypertrophic chondrocyte-like cells that expressed tissue non-specific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which are two key enzymes of the mineralization process. Calcific deposits were composed of apatite crystals associated with proteins involved in bone and cartilage development and endochondral bone growth. In vitro, tenocyte-like cells extracted from the rotator cuff were able to mineralize in osteogenic cultures, and expressed TNAP, type X COLLAGEN, and MMP13, which are hypertrophic chondrocytes markers. The use of a TNAP inhibitor significantly prevented mineral deposits. We provide evidence that tenocytes have a propensity to differentiate into hypertrophic chondrocyte-like cells to produce TNAP-dependent calcium deposits. We believe that these results may pave the way to identifying regulating factors that might represent valuable targets in calcific tendonitis. |
Bhalla, Pratibha; Vernekar, Dipti Vinayak; Gilquin, Benoit; Couté, Yohann; Bhargava, Purnima Interactome of the yeast RNA polymerase III transcription machinery constitutes several chromatin modifiers and regulators of the genes transcribed by RNA polymerase II Article de journal Gene, 702 , p. 205–214, 2019, ISSN: 1879-0038. @article{bhalla_interactome_2019, title = {Interactome of the yeast RNA polymerase III transcription machinery constitutes several chromatin modifiers and regulators of the genes transcribed by RNA polymerase II}, author = {Pratibha Bhalla and Dipti Vinayak Vernekar and Benoit Gilquin and Yohann Couté and Purnima Bhargava}, doi = {10.1016/j.gene.2018.12.037}, issn = {1879-0038}, year = {2019}, date = {2019-01-01}, journal = {Gene}, volume = {702}, pages = {205--214}, abstract = {Eukaryotic transcription is a highly regulated fundamental life process. A large number of regulatory proteins and complexes, many of them with sequence-specific DNA-binding activity are known to influence transcription by RNA polymerase (pol) II with a fine precision. In comparison, only a few regulatory proteins are known for pol III, which transcribes genes encoding small, stable, non-translated RNAs. The pol III transcription is precisely regulated under various stress conditions. We used pol III transcription complex (TC) components TFIIIC (Tfc6), pol III (Rpc128) and TFIIIB (Brf1) as baits and mass spectrometry to identify their potential interactors in vivo. A large interactome constituting chromatin modifiers, regulators and factors of transcription by pol I and pol II supports the possibility of a crosstalk between the three transcription machineries. The association of proteins and complexes involved in various basic life processes like ribogenesis, RNA processing, protein folding and degradation, DNA damage response, replication and transcription underscores the possibility of the pol III TC serving as a signaling hub for communication between the transcription and other cellular physiological activities under normal growth conditions. We also found an equally large number of proteins and complexes interacting with the TC under nutrient starvation condition, of which at least 25% were non-identical under the two conditions. The data reveal the possibility of a large number of signaling cues for pol III transcription against adverse conditions, necessary for an efficient co-ordination of various cellular functions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Eukaryotic transcription is a highly regulated fundamental life process. A large number of regulatory proteins and complexes, many of them with sequence-specific DNA-binding activity are known to influence transcription by RNA polymerase (pol) II with a fine precision. In comparison, only a few regulatory proteins are known for pol III, which transcribes genes encoding small, stable, non-translated RNAs. The pol III transcription is precisely regulated under various stress conditions. We used pol III transcription complex (TC) components TFIIIC (Tfc6), pol III (Rpc128) and TFIIIB (Brf1) as baits and mass spectrometry to identify their potential interactors in vivo. A large interactome constituting chromatin modifiers, regulators and factors of transcription by pol I and pol II supports the possibility of a crosstalk between the three transcription machineries. The association of proteins and complexes involved in various basic life processes like ribogenesis, RNA processing, protein folding and degradation, DNA damage response, replication and transcription underscores the possibility of the pol III TC serving as a signaling hub for communication between the transcription and other cellular physiological activities under normal growth conditions. We also found an equally large number of proteins and complexes interacting with the TC under nutrient starvation condition, of which at least 25% were non-identical under the two conditions. The data reveal the possibility of a large number of signaling cues for pol III transcription against adverse conditions, necessary for an efficient co-ordination of various cellular functions. |
Jeudy, Sandra; Bertaux, Lionel; Alempic, Jean-Marie; Lartigue, Audrey; Legendre, Matthieu; Belmudes, Lucid; Santini, Sébastien; è, Nad; Beucher, Laure; Biondi, Emanuele G; Juul, Sissel; Turner, Daniel J; Couté, Yohann; Claverie, Jean-Michel; Abergel, Chantal Exploration of the propagation of transpovirons within Mimiviridae reveals a unique example of commensalism in the viral world Article de journal The ISME journal, 2019, ISSN: 1751-7370. @article{jeudy_exploration_2019, title = {Exploration of the propagation of transpovirons within Mimiviridae reveals a unique example of commensalism in the viral world}, author = {Sandra Jeudy and Lionel Bertaux and Jean-Marie Alempic and Audrey Lartigue and Matthieu Legendre and Lucid Belmudes and Sébastien Santini and Nad{è}ge Philippe and Laure Beucher and Emanuele G Biondi and Sissel Juul and Daniel J Turner and Yohann Couté and Jean-Michel Claverie and Chantal Abergel}, doi = {10.1038/s41396-019-0565-y}, issn = {1751-7370}, year = {2019}, date = {2019-01-01}, journal = {The ISME journal}, abstract = {Acanthamoeba-infecting Mimiviridae are giant viruses with dsDNA genome up to 1.5 Mb. They build viral factories in the host cytoplasm in which the nuclear-like virus-encoded functions take place. They are themselves the target of infections by 20-kb-dsDNA virophages, replicating in the giant virus factories and can also be found associated with 7-kb-DNA episomes, dubbed transpovirons. Here we isolated a virophage (Zamilon vitis) and two transpovirons respectively associated to B- and C-clade mimiviruses. We found that the virophage could transfer each transpoviron provided the host viruses were devoid of a resident transpoviron (permissive effect). If not, only the resident transpoviron originally isolated from the corresponding virus was replicated and propagated within the virophage progeny (dominance effect). Although B- and C-clade viruses devoid of transpoviron could replicate each transpoviron, they did it with a lower efficiency across clades, suggesting an ongoing process of adaptive co-evolution. We analysed the proteomes of host viruses and virophage particles in search of proteins involved in this adaptation process. This study also highlights a unique example of intricate commensalism in the viral world, where the transpoviron uses the virophage to propagate and where the Zamilon virophage and the transpoviron depend on the giant virus to replicate, without affecting its infectious cycle.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Acanthamoeba-infecting Mimiviridae are giant viruses with dsDNA genome up to 1.5 Mb. They build viral factories in the host cytoplasm in which the nuclear-like virus-encoded functions take place. They are themselves the target of infections by 20-kb-dsDNA virophages, replicating in the giant virus factories and can also be found associated with 7-kb-DNA episomes, dubbed transpovirons. Here we isolated a virophage (Zamilon vitis) and two transpovirons respectively associated to B- and C-clade mimiviruses. We found that the virophage could transfer each transpoviron provided the host viruses were devoid of a resident transpoviron (permissive effect). If not, only the resident transpoviron originally isolated from the corresponding virus was replicated and propagated within the virophage progeny (dominance effect). Although B- and C-clade viruses devoid of transpoviron could replicate each transpoviron, they did it with a lower efficiency across clades, suggesting an ongoing process of adaptive co-evolution. We analysed the proteomes of host viruses and virophage particles in search of proteins involved in this adaptation process. This study also highlights a unique example of intricate commensalism in the viral world, where the transpoviron uses the virophage to propagate and where the Zamilon virophage and the transpoviron depend on the giant virus to replicate, without affecting its infectious cycle. |
Dell'Aglio, Elisa; Giustini, Cecile; Kraut, Alexandra; Couté, Yohann; Costa, Alex; Decros, Guillaume; Gibon, Yves; Mazars, Christian; Matringe, Michel; Finazzi, Giovanni; Curien, Gilles Identification of the Arabidopsis calmodulin-dependent NAD+ kinase that sustains the elicitor-induced oxidative burst Article de journal Plant Physiology, 2019, ISSN: 1532-2548. @article{dellaglio_identification_2019, title = {Identification of the Arabidopsis calmodulin-dependent NAD+ kinase that sustains the elicitor-induced oxidative burst}, author = {Elisa Dell'Aglio and Cecile Giustini and Alexandra Kraut and Yohann Couté and Alex Costa and Guillaume Decros and Yves Gibon and Christian Mazars and Michel Matringe and Giovanni Finazzi and Gilles Curien}, doi = {10.1104/pp.19.00912}, issn = {1532-2548}, year = {2019}, date = {2019-01-01}, journal = {Plant Physiology}, abstract = {NADP(H) is an essential cofactor of multiple metabolic processes in all living organisms, and in plants, NADP(H) is required as the substrate of Ca2+-dependent NADPH oxidases, which catalyze a reactive oxygen species burst in response to various stimuli. While NADP+ production in plants has long been known to involve a calmodulin (CaM)/Ca2+- dependent NAD+ kinase, the nature of the enzyme catalyzing this activity has remained enigmatic, as has its role in plant physiology. Here, we used proteomic, biochemical, molecular and in vivo analyses to identify an Arabidopsis (Arabidopsis thaliana) protein that catalyzes NADP+ production exclusively in the presence of CaM/Ca2+. This enzyme, which we named NAD kinase-CaM dependent (NADKc), has a CaM-binding peptide located in its N-terminal region and displays peculiar biochemical properties as well as different domain organization compared to known plant NAD+ kinases. In response to a pathogen elicitor, activity of NADKc, which is associated with the mitochondrial periphery, contributes to an increase in the cellular NADP+ concentration and to the amplification of the elicitor-induced oxidative burst. Based on a phylogenetic analysis and enzymatic assays, we propose the CaM/Ca2+-dependent NAD+ kinase activity found in photosynthetic organisms is carried out by NADKc-related proteins. Thus, NADKc represents the missing link between Ca2+ signalling, metabolism and the oxidative burst.}, keywords = {}, pubstate = {published}, tppubtype = {article} } NADP(H) is an essential cofactor of multiple metabolic processes in all living organisms, and in plants, NADP(H) is required as the substrate of Ca2+-dependent NADPH oxidases, which catalyze a reactive oxygen species burst in response to various stimuli. While NADP+ production in plants has long been known to involve a calmodulin (CaM)/Ca2+- dependent NAD+ kinase, the nature of the enzyme catalyzing this activity has remained enigmatic, as has its role in plant physiology. Here, we used proteomic, biochemical, molecular and in vivo analyses to identify an Arabidopsis (Arabidopsis thaliana) protein that catalyzes NADP+ production exclusively in the presence of CaM/Ca2+. This enzyme, which we named NAD kinase-CaM dependent (NADKc), has a CaM-binding peptide located in its N-terminal region and displays peculiar biochemical properties as well as different domain organization compared to known plant NAD+ kinases. In response to a pathogen elicitor, activity of NADKc, which is associated with the mitochondrial periphery, contributes to an increase in the cellular NADP+ concentration and to the amplification of the elicitor-induced oxidative burst. Based on a phylogenetic analysis and enzymatic assays, we propose the CaM/Ca2+-dependent NAD+ kinase activity found in photosynthetic organisms is carried out by NADKc-related proteins. Thus, NADKc represents the missing link between Ca2+ signalling, metabolism and the oxidative burst. |
Chapelle, Jennifer; Sorokina, Oksana; McLean, Colin; Salemme, Vincenzo; Alfieri, Annalisa; Angelini, Costanza; Morellato, Alessandro; Adrait, Annie; Menna, Elisabetta; Matteoli, Michela; Couté, Yohann; Ala, Ugo; Turco, Emilia; Defilippi, Paola; Armstrong, Douglas J Dissecting the Shared and Context-Dependent Pathways Mediated by the p140Cap Adaptor Protein in Cancer and in Neurons Article de journal Frontiers in Cell and Developmental Biology, 7 , p. 222, 2019, ISSN: 2296-634X. @article{chapelle_dissecting_2019, title = {Dissecting the Shared and Context-Dependent Pathways Mediated by the p140Cap Adaptor Protein in Cancer and in Neurons}, author = {Jennifer Chapelle and Oksana Sorokina and Colin McLean and Vincenzo Salemme and Annalisa Alfieri and Costanza Angelini and Alessandro Morellato and Annie Adrait and Elisabetta Menna and Michela Matteoli and Yohann Couté and Ugo Ala and Emilia Turco and Paola Defilippi and Douglas J Armstrong}, url = {https://www.frontiersin.org/article/10.3389/fcell.2019.00222/full}, doi = {10.3389/fcell.2019.00222}, issn = {2296-634X}, year = {2019}, date = {2019-01-01}, journal = {Frontiers in Cell and Developmental Biology}, volume = {7}, pages = {222}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Sonego, Maura; Pellarin, Ilenia; Costa, Alice; Vinciguerra, Gian Luca Rampioni; Coan, Michela; Kraut, Alexandra; D'Andrea, Sara; Dall'Acqua, Alessandra; Castillo-Tong, Dan Cacsire; Califano, Daniela; Losito, Simona; Spizzo, Riccardo; Couté, Yohann; Vecchione, Andrea; Belletti, Barbara; Schiappacassi, Monica; Baldassarre, Gustavo USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability Article de journal Science Advances, 5 (5), p. eaav3235, 2019, ISSN: 2375-2548. @article{sonego_usp1_2019, title = {USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability}, author = {Maura Sonego and Ilenia Pellarin and Alice Costa and Gian Luca Rampioni Vinciguerra and Michela Coan and Alexandra Kraut and Sara D'Andrea and Alessandra Dall'Acqua and Dan Cacsire Castillo-Tong and Daniela Califano and Simona Losito and Riccardo Spizzo and Yohann Couté and Andrea Vecchione and Barbara Belletti and Monica Schiappacassi and Gustavo Baldassarre}, doi = {10.1126/sciadv.aav3235}, issn = {2375-2548}, year = {2019}, date = {2019-01-01}, journal = {Science Advances}, volume = {5}, number = {5}, pages = {eaav3235}, abstract = {Resistance to platinum-based chemotherapy is a common event in patients with cancer, generally associated with tumor dissemination and metastasis. Whether platinum treatment per se activates molecular pathways linked to tumor spreading is not known. Here, we report that the ubiquitin-specific protease 1 (USP1) mediates ovarian cancer cell resistance to platinum, by regulating the stability of Snail, which, in turn, promotes tumor dissemination. At the molecular level, we observed that upon platinum treatment, USP1 is phosphorylated by ATM and ATR and binds to Snail. Then, USP1 de-ubiquitinates and stabilizes Snail expression, conferring resistance to platinum, increased stem cell-like features, and metastatic ability. Consistently, knockout or pharmacological inhibition of USP1 increased platinum sensitivity and decreased metastatic dissemination in a Snail-dependent manner. Our findings identify Snail as a USP1 target and open the way to a novel strategy to overcome platinum resistance and more successfully treat patients with ovarian cancer.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Resistance to platinum-based chemotherapy is a common event in patients with cancer, generally associated with tumor dissemination and metastasis. Whether platinum treatment per se activates molecular pathways linked to tumor spreading is not known. Here, we report that the ubiquitin-specific protease 1 (USP1) mediates ovarian cancer cell resistance to platinum, by regulating the stability of Snail, which, in turn, promotes tumor dissemination. At the molecular level, we observed that upon platinum treatment, USP1 is phosphorylated by ATM and ATR and binds to Snail. Then, USP1 de-ubiquitinates and stabilizes Snail expression, conferring resistance to platinum, increased stem cell-like features, and metastatic ability. Consistently, knockout or pharmacological inhibition of USP1 increased platinum sensitivity and decreased metastatic dissemination in a Snail-dependent manner. Our findings identify Snail as a USP1 target and open the way to a novel strategy to overcome platinum resistance and more successfully treat patients with ovarian cancer. |
Louwagie, Mathilde; Kieffer-Jaquinod, Sylvie; Brun, Virginie Ultrasensitive Quantification of Recombinant Proteins Using AAA-MS Article de journal Methods in Molecular Biology (Clifton, N.J.), 2030 , p. 1–10, 2019, ISSN: 1940-6029. @article{louwagie_ultrasensitive_2019, title = {Ultrasensitive Quantification of Recombinant Proteins Using AAA-MS}, author = {Mathilde Louwagie and Sylvie Kieffer-Jaquinod and Virginie Brun}, doi = {10.1007/978-1-4939-9639-1_1}, issn = {1940-6029}, year = {2019}, date = {2019-01-01}, journal = {Methods in Molecular Biology (Clifton, N.J.)}, volume = {2030}, pages = {1--10}, abstract = {Recombinant proteins are essential components of therapeutic, biotechnological, food, and household products. In some cases, recombinant proteins must be purified and their quantity and/or concentration precisely determined. In this chapter, we describe a protocol for the quantification of purified recombinant proteins. The protocol is based on a microwave-assisted acidic hydrolysis of the target protein followed by high-resolution mass spectrometry (HRMS) analysis of the hydrolytic products. Absolute quantification is obtained by adding controlled amounts of labeled amino acids that serve as standards.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Recombinant proteins are essential components of therapeutic, biotechnological, food, and household products. In some cases, recombinant proteins must be purified and their quantity and/or concentration precisely determined. In this chapter, we describe a protocol for the quantification of purified recombinant proteins. The protocol is based on a microwave-assisted acidic hydrolysis of the target protein followed by high-resolution mass spectrometry (HRMS) analysis of the hydrolytic products. Absolute quantification is obtained by adding controlled amounts of labeled amino acids that serve as standards. |
Chiumento, Steve; Roblin, Clarisse; Kieffer-Jaquinod, Sylvie; Tachon, Sybille; è, Chloé Lepr; Basset, Christian; Aditiyarini, Dwi; Olleik, Hamza; Nicoletti, Cendrine; Bornet, Olivier; Iranzo, Olga; Maresca, Marc; Hardré, Renaud; Fons, Michel; Giardina, Thierry; Devillard, Estelle; ç, Fran; Couté, Yohann; Atta, Mohamed; Perrier, Josette; Lafond, Mickael; Duarte, Victor Ruminococcin C, a promising antibiotic produced by a human gut symbiont Article de journal Science Advances, 5 (9), p. eaaw9969, 2019, ISSN: 2375-2548. @article{chiumento_ruminococcin_2019, title = {Ruminococcin C, a promising antibiotic produced by a human gut symbiont}, author = {Steve Chiumento and Clarisse Roblin and Sylvie Kieffer-Jaquinod and Sybille Tachon and Chloé Lepr{è}tre and Christian Basset and Dwi Aditiyarini and Hamza Olleik and Cendrine Nicoletti and Olivier Bornet and Olga Iranzo and Marc Maresca and Renaud Hardré and Michel Fons and Thierry Giardina and Estelle Devillard and Fran{ç}oise Guerlesquin and Yohann Couté and Mohamed Atta and Josette Perrier and Mickael Lafond and Victor Duarte}, doi = {10.1126/sciadv.aaw9969}, issn = {2375-2548}, year = {2019}, date = {2019-01-01}, journal = {Science Advances}, volume = {5}, number = {9}, pages = {eaaw9969}, abstract = {A major public health challenge today is the resurgence of microbial infections caused by multidrug-resistant strains. Consequently, novel antimicrobial molecules are actively sought for development. In this context, the human gut microbiome is an under-explored potential trove of valuable natural molecules, such as the ribosomally-synthesized and post-translationally modified peptides (RiPPs). The biological activity of the sactipeptide subclass of RiPPs remains under-characterized. Here, we characterize an antimicrobial sactipeptide, Ruminococcin C1, purified from the caecal contents of rats mono-associated with Ruminococcus gnavus E1, a human symbiont. Its heterologous expression and post-translational maturation involving a specific sactisynthase establish a thioether network, which creates a double-hairpin folding. This original structure confers activity against pathogenic Clostridia and multidrug-resistant strains but no toxicity towards eukaryotic cells. Therefore, the Ruminococcin C1 should be considered as a valuable candidate for drug development and its producer strain R. gnavus E1 as a relevant probiotic for gut health enhancement.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A major public health challenge today is the resurgence of microbial infections caused by multidrug-resistant strains. Consequently, novel antimicrobial molecules are actively sought for development. In this context, the human gut microbiome is an under-explored potential trove of valuable natural molecules, such as the ribosomally-synthesized and post-translationally modified peptides (RiPPs). The biological activity of the sactipeptide subclass of RiPPs remains under-characterized. Here, we characterize an antimicrobial sactipeptide, Ruminococcin C1, purified from the caecal contents of rats mono-associated with Ruminococcus gnavus E1, a human symbiont. Its heterologous expression and post-translational maturation involving a specific sactisynthase establish a thioether network, which creates a double-hairpin folding. This original structure confers activity against pathogenic Clostridia and multidrug-resistant strains but no toxicity towards eukaryotic cells. Therefore, the Ruminococcin C1 should be considered as a valuable candidate for drug development and its producer strain R. gnavus E1 as a relevant probiotic for gut health enhancement. |
Nguyen, Lien; Brun, Virginie; Combes, Florence; Loux, Valentin; Vandenbrouck, Yves Designing an In Silico Strategy to Select Tissue-Leakage Biomarkers Using the Galaxy Framework Article de journal Methods in Molecular Biology (Clifton, N.J.), 1959 , p. 275–289, 2019, ISSN: 1940-6029. @article{nguyen_designing_2019, title = {Designing an In Silico Strategy to Select Tissue-Leakage Biomarkers Using the Galaxy Framework}, author = {Lien Nguyen and Virginie Brun and Florence Combes and Valentin Loux and Yves Vandenbrouck}, doi = {10.1007/978-1-4939-9164-8_18}, issn = {1940-6029}, year = {2019}, date = {2019-01-01}, journal = {Methods in Molecular Biology (Clifton, N.J.)}, volume = {1959}, pages = {275--289}, abstract = {Knowledge-based approaches using large-scale biological ("omics") data are a powerful way to identify mechanistic biomarkers, provided that scientists have access to computational solutions even when they have little programming experience or bioinformatics support. To achieve this goal, we designed a set of tools under the Galaxy framework to allow biologists to define their own strategy for reproducible biomarker selection. These tools rely on retrieving experimental data from public databases, and applying successive filters derived from information relating to disease pathophysiology. A step-by-step protocol linking these tools was implemented to select tissue-leakage biomarker candidates of myocardial infarction. A list of 24 candidates suitable for experimental assessment by MS-based proteomics is proposed. These tools have been made publicly available at http://www.proteore.org , allowing researchers to reuse them in their quest for biomarker discovery.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Knowledge-based approaches using large-scale biological ("omics") data are a powerful way to identify mechanistic biomarkers, provided that scientists have access to computational solutions even when they have little programming experience or bioinformatics support. To achieve this goal, we designed a set of tools under the Galaxy framework to allow biologists to define their own strategy for reproducible biomarker selection. These tools rely on retrieving experimental data from public databases, and applying successive filters derived from information relating to disease pathophysiology. A step-by-step protocol linking these tools was implemented to select tissue-leakage biomarker candidates of myocardial infarction. A list of 24 candidates suitable for experimental assessment by MS-based proteomics is proposed. These tools have been made publicly available at http://www.proteore.org , allowing researchers to reuse them in their quest for biomarker discovery. |
Beurton, Flore; Stempor, Przemyslaw; Caron, Matthieu; Appert, Alex; Dong, Yan; Chen, Ron A -J; Cluet, David; Couté, Yohann; Herbette, Marion; Huang, Ni; è, Hél; Spichty, Martin; Bedet, Cécile; Ahringer, Julie; Palladino, Francesca Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans Article de journal Nucleic Acids Research, 2019, ISSN: 1362-4962. @article{beurton_physical_2019, title = {Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans}, author = {Flore Beurton and Przemyslaw Stempor and Matthieu Caron and Alex Appert and Yan Dong and Ron A -J Chen and David Cluet and Yohann Couté and Marion Herbette and Ni Huang and Hél{è}ne Polveche and Martin Spichty and Cécile Bedet and Julie Ahringer and Francesca Palladino}, doi = {10.1093/nar/gkz880}, issn = {1362-4962}, year = {2019}, date = {2019-01-01}, journal = {Nucleic Acids Research}, abstract = {The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to non-methylated CpG rich promoters to implement tri-methylation of histone H3 Lys4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss vary, suggesting additional chromatin factors contribute to context dependent effects. Using a proteomics approach, we identified CFP1 associated proteins and an unexpected direct link between Caenorhabditis elegans CFP-1 and an Rpd3/Sin3 small (SIN3S) histone deacetylase complex. Supporting a functional connection, we find that mutants of COMPASS and SIN3 complex components genetically interact and have similar phenotypic defects including misregulation of common genes. CFP-1 directly binds SIN-3 through a region including the conserved PAH1 domain and recruits SIN-3 and the HDA-1/HDAC subunit to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3S HDAC complex at promoters.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to non-methylated CpG rich promoters to implement tri-methylation of histone H3 Lys4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss vary, suggesting additional chromatin factors contribute to context dependent effects. Using a proteomics approach, we identified CFP1 associated proteins and an unexpected direct link between Caenorhabditis elegans CFP-1 and an Rpd3/Sin3 small (SIN3S) histone deacetylase complex. Supporting a functional connection, we find that mutants of COMPASS and SIN3 complex components genetically interact and have similar phenotypic defects including misregulation of common genes. CFP-1 directly binds SIN-3 through a region including the conserved PAH1 domain and recruits SIN-3 and the HDA-1/HDAC subunit to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3S HDAC complex at promoters. |
è, Hél; Guibert, Romain; Permiakova, Olga; Burger, Thomas Distinguishing between Spectral Clustering and Cluster Analysis of Mass Spectra Article de journal Journal of Proteome Research, 18 (1), p. 571–573, 2019, ISSN: 1535-3907. @article{borges_distinguishing_2019, title = {Distinguishing between Spectral Clustering and Cluster Analysis of Mass Spectra}, author = {Hél{è}ne Borges and Romain Guibert and Olga Permiakova and Thomas Burger}, doi = {10.1021/acs.jproteome.8b00516}, issn = {1535-3907}, year = {2019}, date = {2019-01-01}, journal = {Journal of Proteome Research}, volume = {18}, number = {1}, pages = {571--573}, abstract = {The term "spectral clustering" is sometimes used to refer to the clustering of mass spectrometry data. However, it also classically refers to a family of popular clustering algorithms. To avoid confusion, a more specific term could advantageously be coined.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The term "spectral clustering" is sometimes used to refer to the clustering of mass spectrometry data. However, it also classically refers to a family of popular clustering algorithms. To avoid confusion, a more specific term could advantageously be coined. |
Wieczorek, Samuel; Combes, Florence; è, Hél; Burger, Thomas Protein-Level Statistical Analysis of Quantitative Label-Free Proteomics Data with ProStaR Article de journal Methods in Molecular Biology (Clifton, N.J.), 1959 , p. 225–246, 2019, ISSN: 1940-6029. @article{wieczorek_protein-level_2019, title = {Protein-Level Statistical Analysis of Quantitative Label-Free Proteomics Data with ProStaR}, author = {Samuel Wieczorek and Florence Combes and Hél{è}ne Borges and Thomas Burger}, doi = {10.1007/978-1-4939-9164-8_15}, issn = {1940-6029}, year = {2019}, date = {2019-01-01}, journal = {Methods in Molecular Biology (Clifton, N.J.)}, volume = {1959}, pages = {225--246}, abstract = {ProStaR is a software tool dedicated to differential analysis in label-free quantitative proteomics. Practically, once biological samples have been analyzed by bottom-up mass spectrometry-based proteomics, the raw mass spectrometer outputs are processed by bioinformatics tools, so as to identify peptides and quantify them, by means of precursor ion chromatogram integration. Then, it is classical to use these peptide-level pieces of information to derive the identity and quantity of the sample proteins before proceeding with refined statistical processing at protein-level, so as to bring out proteins which abundance is significantly different between different groups of samples. To achieve this statistical step, it is possible to rely on ProStaR, which allows the user to (1) load correctly formatted data, (2) clean them by means of various filters, (3) normalize the sample batches, (4) impute the missing values, (5) perform null hypothesis significance testing, (6) check the well-calibration of the resulting p-values, (7) select a subset of differentially abundant proteins according to some false discovery rate, and (8) contextualize these selected proteins into the Gene Ontology. This chapter provides a detailed protocol on how to perform these eight processing steps with ProStaR.}, keywords = {}, pubstate = {published}, tppubtype = {article} } ProStaR is a software tool dedicated to differential analysis in label-free quantitative proteomics. Practically, once biological samples have been analyzed by bottom-up mass spectrometry-based proteomics, the raw mass spectrometer outputs are processed by bioinformatics tools, so as to identify peptides and quantify them, by means of precursor ion chromatogram integration. Then, it is classical to use these peptide-level pieces of information to derive the identity and quantity of the sample proteins before proceeding with refined statistical processing at protein-level, so as to bring out proteins which abundance is significantly different between different groups of samples. To achieve this statistical step, it is possible to rely on ProStaR, which allows the user to (1) load correctly formatted data, (2) clean them by means of various filters, (3) normalize the sample batches, (4) impute the missing values, (5) perform null hypothesis significance testing, (6) check the well-calibration of the resulting p-values, (7) select a subset of differentially abundant proteins according to some false discovery rate, and (8) contextualize these selected proteins into the Gene Ontology. This chapter provides a detailed protocol on how to perform these eight processing steps with ProStaR. |
Pinaud, Silvain; ï, Ana; ç, Jean-Fran; Belmudes, Lucid; Saint-Beat, Cécile; Arancibia, Nathalie; Galinier, Richard; Du Pasquier, Louis ; Duval, David; Gourbal, Benjamin Molecular characterisation of immunological memory following homologous or heterologous challenges in the schistosomiasis vector snail, Biomphalaria glabrata Article de journal Developmental and Comparative Immunology, 92 , p. 238–252, 2019, ISSN: 1879-0089. @article{pinaud_molecular_2019, title = {Molecular characterisation of immunological memory following homologous or heterologous challenges in the schistosomiasis vector snail, Biomphalaria glabrata}, author = {Silvain Pinaud and Ana{ï}s Portet and Jean-Fran{ç}ois Allienne and Lucid Belmudes and Cécile Saint-Beat and Nathalie Arancibia and Richard Galinier and Louis {Du Pasquier} and David Duval and Benjamin Gourbal}, doi = {10.1016/j.dci.2018.12.001}, issn = {1879-0089}, year = {2019}, date = {2019-01-01}, journal = {Developmental and Comparative Immunology}, volume = {92}, pages = {238--252}, abstract = {Invertebrate immune response may be primed by a current infection in a sustained manner, leading to the failure of a secondary infection with the same pathogen. The present study focuses on the Schistosomiasis vector snail Biomphalaria glabrata, in which a specific genotype-dependent immunological memory was demonstrated as a shift from a cellular to a humoral immune response. Herein, we investigate the complex molecular bases associated with this genotype-dependant immunological memory response. We demonstrate that Biomphalaria regulates a polymorphic set of immune recognition molecules and immune effector repertoires to respond to different strains of Schistosoma parasites. These results suggest a combinatorial usage of pathogen recognition receptors (PRRs) that distinguish different strains of parasites during the acquisition of immunological memory. Immunizations also show that snails become resistant after exposure to parasite extracts. Hemolymph transfer and a label-free proteomic analysis proved that circulating hemolymph compounds can be produced and released to more efficiently kill the newly encountered parasite of the same genetic lineage.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Invertebrate immune response may be primed by a current infection in a sustained manner, leading to the failure of a secondary infection with the same pathogen. The present study focuses on the Schistosomiasis vector snail Biomphalaria glabrata, in which a specific genotype-dependent immunological memory was demonstrated as a shift from a cellular to a humoral immune response. Herein, we investigate the complex molecular bases associated with this genotype-dependant immunological memory response. We demonstrate that Biomphalaria regulates a polymorphic set of immune recognition molecules and immune effector repertoires to respond to different strains of Schistosoma parasites. These results suggest a combinatorial usage of pathogen recognition receptors (PRRs) that distinguish different strains of parasites during the acquisition of immunological memory. Immunizations also show that snails become resistant after exposure to parasite extracts. Hemolymph transfer and a label-free proteomic analysis proved that circulating hemolymph compounds can be produced and released to more efficiently kill the newly encountered parasite of the same genetic lineage. |
Deutsch, Eric W; Lane, Lydie; Overall, Christopher M; Bandeira, Nuno; Baker, Mark S; Pineau, Charles; Moritz, Robert L; Corrales, Fernando; Orchard, Sandra; Van Eyk, Jennifer E; Paik, Young-Ki; Weintraub, Susan T; Vandenbrouck, Yves; Omenn, Gilbert S Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 3.0 Article de journal Journal of Proteome Research, 2019, ISSN: 1535-3907. @article{deutsch_human_2019, title = {Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 3.0}, author = {Eric W Deutsch and Lydie Lane and Christopher M Overall and Nuno Bandeira and Mark S Baker and Charles Pineau and Robert L Moritz and Fernando Corrales and Sandra Orchard and Jennifer E {Van Eyk} and Young-Ki Paik and Susan T Weintraub and Yves Vandenbrouck and Gilbert S Omenn}, doi = {10.1021/acs.jproteome.9b00542}, issn = {1535-3907}, year = {2019}, date = {2019-01-01}, journal = {Journal of Proteome Research}, abstract = {The Human Proteome Organization's (HUPO) Human Proteome Project (HPP) developed Mass Spectrometry (MS) Data Interpretation Guidelines that have been applied since 2016. These guidelines have helped ensure that the emerging draft of the complete human proteome is highly accurate and with low numbers of false-positive protein identifications. Here, we describe an update to these guidelines based on consensus-reaching discussions with the wider HPP community over the past year. The revised 3.0 guidelines address several major and minor identified gaps. We have added guidelines for emerging data independent acquisition (DIA) MS workflows and for use of the new Universal Spectrum Identifier (USI) system being developed by the HUPO Proteomics Standards Initiative (PSI). In addition, we discuss updates to the standard HPP pipeline for collecting MS evidence for all proteins in the HPP, including refinements to minimum evidence. We present a new plan for incorporating MassIVE-KB into the HPP pipeline for the next (HPP 2020) cycle in order to obtain more comprehensive coverage of public MS data sets. The main checklist has been reorganized under headings and subitems, and related guidelines have been grouped. In sum, Version 2.1 of the HPP MS Data Interpretation Guidelines has served well, and this timely update to version 3.0 will aid the HPP as it approaches its goal of collecting and curating MS evidence of translation and expression for all predicted ∼20 000 human proteins encoded by the human genome.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Human Proteome Organization's (HUPO) Human Proteome Project (HPP) developed Mass Spectrometry (MS) Data Interpretation Guidelines that have been applied since 2016. These guidelines have helped ensure that the emerging draft of the complete human proteome is highly accurate and with low numbers of false-positive protein identifications. Here, we describe an update to these guidelines based on consensus-reaching discussions with the wider HPP community over the past year. The revised 3.0 guidelines address several major and minor identified gaps. We have added guidelines for emerging data independent acquisition (DIA) MS workflows and for use of the new Universal Spectrum Identifier (USI) system being developed by the HUPO Proteomics Standards Initiative (PSI). In addition, we discuss updates to the standard HPP pipeline for collecting MS evidence for all proteins in the HPP, including refinements to minimum evidence. We present a new plan for incorporating MassIVE-KB into the HPP pipeline for the next (HPP 2020) cycle in order to obtain more comprehensive coverage of public MS data sets. The main checklist has been reorganized under headings and subitems, and related guidelines have been grouped. In sum, Version 2.1 of the HPP MS Data Interpretation Guidelines has served well, and this timely update to version 3.0 will aid the HPP as it approaches its goal of collecting and curating MS evidence of translation and expression for all predicted ∼20 000 human proteins encoded by the human genome. |
2018 |
Boeuf, A; Schnell, G; Bernard, Q; Kern, A; Westermann, B; Ehret-Sabatier, L; Grillon, A; Schramm, F; Jaulhac, B; Boulanger, N Dissociating effect of salivary gland extract from Ixodes ricinus on human fibroblasts: Potential impact on Borrelia transmission Article de journal Ticks Tick Borne Dis., 10 (2), p. 433–441, 2018, (2012/29). @article{626b, title = {Dissociating effect of salivary gland extract from Ixodes ricinus on human fibroblasts: Potential impact on Borrelia transmission}, author = {A Boeuf and G Schnell and Q Bernard and A Kern and B Westermann and L Ehret-Sabatier and A Grillon and F Schramm and B Jaulhac and N Boulanger}, doi = {10.1016/j.ttbdis.2018.12.005}, year = {2018}, date = {2018-12-23}, journal = {Ticks Tick Borne Dis.}, volume = {10}, number = {2}, pages = {433–441}, note = {2012/29}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Tascher, G; Gerbaix, M; Maes, P; Chazarin, B; Ghislin, S; Antropova, E; Vassilieva, G; Ouzren-Zarhloul, N; Gauquelin-Koch, G; Vico, L; Frippiat, JP.; Bertile, F Analysis of femurs from mice embarked on board BION-M1 biosatellite reveals a decrease in immune cell development, including B cells, after 1 wk of recovery on Earth Article de journal FASEB J., 33 (3), 2018. @article{625b, title = {Analysis of femurs from mice embarked on board BION-M1 biosatellite reveals a decrease in immune cell development, including B cells, after 1 wk of recovery on Earth}, author = {G Tascher and M Gerbaix and P Maes and B Chazarin and S Ghislin and E Antropova and G Vassilieva and N Ouzren-Zarhloul and G Gauquelin-Koch and L Vico and JP. Frippiat and F Bertile}, doi = {10.1096/fj.201801463R}, year = {2018}, date = {2018-12-06}, journal = {FASEB J.}, volume = {33}, number = {3}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Jonckheere, Julie; Deloulme, Jean-Christophe; Dall'Igna, Gaëlle; Chauliac, Nicolas; Pelluet, Albane; Nguon, Anne-Sophie; Lentini, Celia; Brocard, Jacques; Denarier, Eric; Brugière, Sabine; Couté, Yohann; Heinrich, Christophe; Porcher, Christophe; Holtzmann, Jérôme; Andrieux, Annie; Suaud-Chagny, Marie-Françoise; Gory-Fauré, Sylvie Short- and long-term efficacy of electroconvulsive stimulation in animal models of depression: The essential role of neuronal survival Article de journal Brain Stimulation, 11 (6), p. 1336–1347, 2018, ISSN: 1876-4754. @article{jonckheere_short-_2018, title = {Short- and long-term efficacy of electroconvulsive stimulation in animal models of depression: The essential role of neuronal survival}, author = {Julie Jonckheere and Jean-Christophe Deloulme and Gaëlle Dall'Igna and Nicolas Chauliac and Albane Pelluet and Anne-Sophie Nguon and Celia Lentini and Jacques Brocard and Eric Denarier and Sabine Brugière and Yohann Couté and Christophe Heinrich and Christophe Porcher and Jérôme Holtzmann and Annie Andrieux and Marie-Françoise Suaud-Chagny and Sylvie Gory-Fauré}, doi = {10.1016/j.brs.2018.08.001}, issn = {1876-4754}, year = {2018}, date = {2018-12-01}, journal = {Brain Stimulation}, volume = {11}, number = {6}, pages = {1336--1347}, abstract = {BACKGROUND: Severe and medication-resistant psychiatric diseases, such as major depressive disorder, bipolar disorder or schizophrenia, can be effectively and rapidly treated by electroconvulsive therapy (ECT). Despite extensive long-standing clinical use, the neurobiological mechanisms underlying the curative action of ECT remain incompletely understood. OBJECTIVE: Unravel biological basis of electroconvulsive stimulation (ECS) efficacy, the animal equivalent of ECT. METHODS: Using MAP6 KO mouse, a genetic model that constitutively exhibits features relevant to some aspects of depression; we analyzed the behavioral and biological consequences of ECS treatment alone (10 stimulations over a 2-week period) and associated with a continuation protocol (2 stimulations per week for 5 weeks). RESULTS: ECS treatment had a beneficial effect on constitutive behavioral defects. We showed that behavioral improvement is associated with a strong increase in the survival and integration of neurons born before ECS treatment. Retroviral infection revealed the larger number of integrated neurons to exhibit increased dendritic complexity and spine density, as well as remodeled synapses. Furthermore, our results show that ECS triggers a cortical increase in synaptogenesis. A sustained newborn neuron survival rate, induced by ECS treatment, is associated with the behavioral improvement, but relapse occurred 40 days after completing the ECS treatment. However, a 5-week continuation protocol following the initial ECS treatment led to persistent improvement of behavior correlated with sustained rate survival of newborn neurons. CONCLUSION: Altogether, these results reveal that increased synaptic connectivity and extended neuronal survival are key to the short and long-term efficacy of ECS.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Severe and medication-resistant psychiatric diseases, such as major depressive disorder, bipolar disorder or schizophrenia, can be effectively and rapidly treated by electroconvulsive therapy (ECT). Despite extensive long-standing clinical use, the neurobiological mechanisms underlying the curative action of ECT remain incompletely understood. OBJECTIVE: Unravel biological basis of electroconvulsive stimulation (ECS) efficacy, the animal equivalent of ECT. METHODS: Using MAP6 KO mouse, a genetic model that constitutively exhibits features relevant to some aspects of depression; we analyzed the behavioral and biological consequences of ECS treatment alone (10 stimulations over a 2-week period) and associated with a continuation protocol (2 stimulations per week for 5 weeks). RESULTS: ECS treatment had a beneficial effect on constitutive behavioral defects. We showed that behavioral improvement is associated with a strong increase in the survival and integration of neurons born before ECS treatment. Retroviral infection revealed the larger number of integrated neurons to exhibit increased dendritic complexity and spine density, as well as remodeled synapses. Furthermore, our results show that ECS triggers a cortical increase in synaptogenesis. A sustained newborn neuron survival rate, induced by ECS treatment, is associated with the behavioral improvement, but relapse occurred 40 days after completing the ECS treatment. However, a 5-week continuation protocol following the initial ECS treatment led to persistent improvement of behavior correlated with sustained rate survival of newborn neurons. CONCLUSION: Altogether, these results reveal that increased synaptic connectivity and extended neuronal survival are key to the short and long-term efficacy of ECS. |
Albaret, Marie Alexandra; Vermot-Desroches, Claudine; Paré, Arnaud; Roca-Martinez, Jean-Xavier; Malet, Lucie; Esseily, Jad; Gerossier, Laetitia; Brière, Johan; Pion, Nathalie; Marcel, Virginie; Catez, Frédéric; Souza, Geneviève De; Vuillermoz, Boris; Doerflinger, Franck; Lavocat, Emilie; Subiger, Olivier; Rousset, Carine; Bresson, Corinne; Mandon, Elodie; Jawhari, Anass; Falson, Pierre; Jasmin, Mélissa; Couté, Yohann; Mertani, Hichem-Claude; Saintigny, Pierre; Diaz, Jean-Jacques Externalized Keratin 8: A Target at the Interface of Microenvironment and Intracellular Signaling in Colorectal Cancer Cells Article de journal Cancers, 10 (11), 2018, ISSN: 2072-6694. @article{albaret_externalized_2018, title = {Externalized Keratin 8: A Target at the Interface of Microenvironment and Intracellular Signaling in Colorectal Cancer Cells}, author = {Marie Alexandra Albaret and Claudine Vermot-Desroches and Arnaud Paré and Jean-Xavier Roca-Martinez and Lucie Malet and Jad Esseily and Laetitia Gerossier and Johan Brière and Nathalie Pion and Virginie Marcel and Frédéric Catez and Geneviève De Souza and Boris Vuillermoz and Franck Doerflinger and Emilie Lavocat and Olivier Subiger and Carine Rousset and Corinne Bresson and Elodie Mandon and Anass Jawhari and Pierre Falson and Mélissa Jasmin and Yohann Couté and Hichem-Claude Mertani and Pierre Saintigny and Jean-Jacques Diaz}, doi = {10.3390/cancers10110452}, issn = {2072-6694}, year = {2018}, date = {2018-11-01}, journal = {Cancers}, volume = {10}, number = {11}, abstract = {Accumulating evidence supports the remarkable presence at the membrane surface of cancer cells of proteins, which are normally expressed in the intracellular compartment. Although these proteins, referred to as externalized proteins, represent a highly promising source of accessible and druggable targets for cancer therapy, the mechanisms via which they impact cancer biology remain largely unexplored. The aim of this study was to expose an externalized form of cytokeratin 8 (eK8) as a key player of colorectal tumorigenesis and characterize its mode of action. To achieve this, we generated a unique antagonist monoclonal antibody (D-A10 MAb) targeting an eight-amino-acid-long domain of eK8, which enabled us to ascertain the pro-tumoral activity of eK8 in both KRAS-mutant and wild-type colorectal cancers (CRC). We showed that this pro-tumoral activity involves a bidirectional eK8-dependent control of caspase-mediated apoptosis in vivo and of the plasminogen-induced invasion process in cellulo. Furthermore, we demonstrated that eK8 is anchored at the plasma membrane supporting this dual function. We, therefore, identified eK8 as an innovative therapeutic target in CRC and provided a unique MAb targeting eK8 that displays anti-neoplastic activities that could be useful to treat CRC, including those harboring KRAS mutations.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Accumulating evidence supports the remarkable presence at the membrane surface of cancer cells of proteins, which are normally expressed in the intracellular compartment. Although these proteins, referred to as externalized proteins, represent a highly promising source of accessible and druggable targets for cancer therapy, the mechanisms via which they impact cancer biology remain largely unexplored. The aim of this study was to expose an externalized form of cytokeratin 8 (eK8) as a key player of colorectal tumorigenesis and characterize its mode of action. To achieve this, we generated a unique antagonist monoclonal antibody (D-A10 MAb) targeting an eight-amino-acid-long domain of eK8, which enabled us to ascertain the pro-tumoral activity of eK8 in both KRAS-mutant and wild-type colorectal cancers (CRC). We showed that this pro-tumoral activity involves a bidirectional eK8-dependent control of caspase-mediated apoptosis in vivo and of the plasminogen-induced invasion process in cellulo. Furthermore, we demonstrated that eK8 is anchored at the plasma membrane supporting this dual function. We, therefore, identified eK8 as an innovative therapeutic target in CRC and provided a unique MAb targeting eK8 that displays anti-neoplastic activities that could be useful to treat CRC, including those harboring KRAS mutations. |
Hahn, Friedrich; Hutterer, Corina; Henry, Christophe; Hamilton, Stuart T; Strojan, Hanife; Kraut, Alexandra; Schulte, Ulrike; Schütz, Martin; Kohrt, Stephan; Wangen, Christina; Pfizer, José; Couté, Yohann; Rawlinson, William D; Strobl, Stefan; Marschall, Manfred Novel cytomegalovirus-inhibitory compounds of the class pyrrolopyridines show a complex pattern of target binding that suggests an unusual mechanism of antiviral activity Article de journal Antiviral Research, 159 , p. 84–94, 2018, ISSN: 1872-9096. @article{hahn_novel_2018, title = {Novel cytomegalovirus-inhibitory compounds of the class pyrrolopyridines show a complex pattern of target binding that suggests an unusual mechanism of antiviral activity}, author = {Friedrich Hahn and Corina Hutterer and Christophe Henry and Stuart T Hamilton and Hanife Strojan and Alexandra Kraut and Ulrike Schulte and Martin Schütz and Stephan Kohrt and Christina Wangen and José Pfizer and Yohann Couté and William D Rawlinson and Stefan Strobl and Manfred Marschall}, doi = {10.1016/j.antiviral.2018.09.012}, issn = {1872-9096}, year = {2018}, date = {2018-11-01}, journal = {Antiviral Research}, volume = {159}, pages = {84--94}, abstract = {Human cytomegalovirus (HCMV) is a major human pathogen with seropositivity rates in the adult population ranging between 40% and 95%. HCMV infection is associated with severe pathology, such as life-threatening courses of infection in immunocompromised individuals and neonates. Current standard therapy with valganciclovir has the disadvantage of adverse side effects and viral drug resistance. A novel anti-HCMV drug, letermovir, has been approved recently, so that improved therapy options are available. Nevertheless, even more so far unexploited classes of compounds and molecular modes of action will be required for a next generation of antiherpesviral treatment strategies. In this study, we focused on the analysis of the antiviral potency of a novel class of compounds, i.e. pyrrolopyridine analogs, and identified both hit compounds and their target protein candidates. In essence, we provide novel evidence as follows: (i) screening hit SC88941 is highly active in inhibiting HCMV replication in primary human fibroblasts with an EC50 value of 0.20 ± 0.01 μM in the absence of cytotoxicity, (ii) inhibition occurs at the early-late stage of viral protein production and shows reinforcing effects upon LMV cotreatment, (iii) among the viruses analyzed, antiviral activity was most pronounced against β-herpesviruses (HCMV, HHV-6A) and intermediate against adenovirus (HAdV-2), (iv) induction of SC88941 resistance was not detectable, thus differed from the induction of ganciclovir resistance, (v) a linker-coupled model compound was used for mass spectrometry-based target identification, thus yielding several drug-binding target proteins and (vi) a first confocal imaging approach used for addressing intracellular effects of SC88941 indicated qualitative and quantitative alteration of viral protein expression and localization. Thus, our findings suggest a multifaceted pattern of compound-target binding in connection with an unusual mode of action, opening up further opportunities of antiviral drug development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Human cytomegalovirus (HCMV) is a major human pathogen with seropositivity rates in the adult population ranging between 40% and 95%. HCMV infection is associated with severe pathology, such as life-threatening courses of infection in immunocompromised individuals and neonates. Current standard therapy with valganciclovir has the disadvantage of adverse side effects and viral drug resistance. A novel anti-HCMV drug, letermovir, has been approved recently, so that improved therapy options are available. Nevertheless, even more so far unexploited classes of compounds and molecular modes of action will be required for a next generation of antiherpesviral treatment strategies. In this study, we focused on the analysis of the antiviral potency of a novel class of compounds, i.e. pyrrolopyridine analogs, and identified both hit compounds and their target protein candidates. In essence, we provide novel evidence as follows: (i) screening hit SC88941 is highly active in inhibiting HCMV replication in primary human fibroblasts with an EC50 value of 0.20 ± 0.01 μM in the absence of cytotoxicity, (ii) inhibition occurs at the early-late stage of viral protein production and shows reinforcing effects upon LMV cotreatment, (iii) among the viruses analyzed, antiviral activity was most pronounced against β-herpesviruses (HCMV, HHV-6A) and intermediate against adenovirus (HAdV-2), (iv) induction of SC88941 resistance was not detectable, thus differed from the induction of ganciclovir resistance, (v) a linker-coupled model compound was used for mass spectrometry-based target identification, thus yielding several drug-binding target proteins and (vi) a first confocal imaging approach used for addressing intracellular effects of SC88941 indicated qualitative and quantitative alteration of viral protein expression and localization. Thus, our findings suggest a multifaceted pattern of compound-target binding in connection with an unusual mode of action, opening up further opportunities of antiviral drug development. |
Borges, Hélène; Guibert, Romain; Permiakova, Olga; Burger, Thomas Distinguishing between Spectral Clustering and Cluster Analysis of Mass Spectra Article de journal Journal of Proteome Research, 2018, ISSN: 1535-3907. @article{borges_distinguishing_2018, title = {Distinguishing between Spectral Clustering and Cluster Analysis of Mass Spectra}, author = {Hélène Borges and Romain Guibert and Olga Permiakova and Thomas Burger}, doi = {10.1021/acs.jproteome.8b00516}, issn = {1535-3907}, year = {2018}, date = {2018-11-01}, journal = {Journal of Proteome Research}, abstract = {The term "spectral clustering" is sometimes used to refer to the clustering of mass spectrometry data. However, it also classically refers to a family of popular clustering algorithms. To avoid confusion, a more specific term could advantageously be coined.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The term "spectral clustering" is sometimes used to refer to the clustering of mass spectrometry data. However, it also classically refers to a family of popular clustering algorithms. To avoid confusion, a more specific term could advantageously be coined. |
Dominguez-Medina, Sergio; Fostner, Shawn; Defoort, Martial; Sansa, Marc; Stark, Ann-Kathrin; Halim, Mohammad Abdul; Vernhes, Emeline; Gely, Marc; Jourdan, Guillaume; Alava, Thomas; Boulanger, Pascale; Masselon, Christophe; Hentz, Sébastien Neutral mass spectrometry of virus capsids above 100 megadaltons with nanomechanical resonators Article de journal Science (New York, N.Y.), 362 (6417), p. 918–922, 2018, ISSN: 1095-9203. @article{dominguez-medina_neutral_2018, title = {Neutral mass spectrometry of virus capsids above 100 megadaltons with nanomechanical resonators}, author = {Sergio Dominguez-Medina and Shawn Fostner and Martial Defoort and Marc Sansa and Ann-Kathrin Stark and Mohammad Abdul Halim and Emeline Vernhes and Marc Gely and Guillaume Jourdan and Thomas Alava and Pascale Boulanger and Christophe Masselon and Sébastien Hentz}, doi = {10.1126/science.aat6457}, issn = {1095-9203}, year = {2018}, date = {2018-11-01}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {918--922}, abstract = {Measurement of the mass of particles in the mega- to gigadalton range is challenging with conventional mass spectrometry. Although this mass range appears optimal for nanomechanical resonators, nanomechanical mass spectrometers often suffer from prohibitive sample loss, extended analysis time, or inadequate resolution. We report on a system architecture combining nebulization of the analytes from solution, their efficient transfer and focusing without relying on electromagnetic fields, and the mass measurements of individual particles using nanomechanical resonator arrays. This system determined the mass distribution of textasciitilde30-megadalton polystyrene nanoparticles with high detection efficiency and effectively performed molecular mass measurements of empty or DNA-filled bacteriophage T5 capsids with masses up to 105 megadaltons using less than 1 picomole of sample and with an instrument resolution above 100.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Measurement of the mass of particles in the mega- to gigadalton range is challenging with conventional mass spectrometry. Although this mass range appears optimal for nanomechanical resonators, nanomechanical mass spectrometers often suffer from prohibitive sample loss, extended analysis time, or inadequate resolution. We report on a system architecture combining nebulization of the analytes from solution, their efficient transfer and focusing without relying on electromagnetic fields, and the mass measurements of individual particles using nanomechanical resonator arrays. This system determined the mass distribution of textasciitilde30-megadalton polystyrene nanoparticles with high detection efficiency and effectively performed molecular mass measurements of empty or DNA-filled bacteriophage T5 capsids with masses up to 105 megadaltons using less than 1 picomole of sample and with an instrument resolution above 100. |
Do, Le Duy; Gupton, Stéphanie L; Tanji, Kunikazu; Bastien, Joubert; Brugière, Sabine; Couté, Yohann; Quadrio, Isabelle; Rogemond, Véronique; Fabien, Nicole; Desestret, Virginie; Honnorat, Jérôme TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration Article de journal Cerebellum (London, England), 2018, ISSN: 1473-4230. @article{do_trim9_2018, title = {TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration}, author = {Le Duy Do and Stéphanie L Gupton and Kunikazu Tanji and Joubert Bastien and Sabine Brugière and Yohann Couté and Isabelle Quadrio and Véronique Rogemond and Nicole Fabien and Virginie Desestret and Jérôme Honnorat}, doi = {10.1007/s12311-018-0987-5}, issn = {1473-4230}, year = {2018}, date = {2018-10-01}, journal = {Cerebellum (London, England)}, abstract = {To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67, and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, 36 patients with lung adenocarcinoma and PNS, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases. We found Abs targeting TRIM9 and TRIM67 at high concentration in the serum and the cerebrospinal fluid (CSF) of a 78-year-old woman and a 65-year-old man. Both developed subacute severe cerebellar ataxia. Brain magnetic resonance imaging found no abnormality and no cerebellar atrophy. Both had CSF inflammation with mild pleiocytosis and a few oligoclonal bands. We identified a pulmonary adenocarcinoma, confirming the paraneoplastic neurological syndrome in both patients. They received immunomodulatory and cancer treatments without improvement of cerebellar ataxia, even though both were in remission of their cancer (for more than 10 years in one patient). Anti-TRIM9 and anti-TRIM67 Abs were specific to these two patients. All control serum and CSF samples tested were negative for anti-TRIM9 and 67. Anti-TRIM9 and anti-TRIM67 Abs appeared to be specific biomarkers of PCD and should be added to the panel of antigens tested when this is suspected.}, keywords = {}, pubstate = {published}, tppubtype = {article} } To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67, and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, 36 patients with lung adenocarcinoma and PNS, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases. We found Abs targeting TRIM9 and TRIM67 at high concentration in the serum and the cerebrospinal fluid (CSF) of a 78-year-old woman and a 65-year-old man. Both developed subacute severe cerebellar ataxia. Brain magnetic resonance imaging found no abnormality and no cerebellar atrophy. Both had CSF inflammation with mild pleiocytosis and a few oligoclonal bands. We identified a pulmonary adenocarcinoma, confirming the paraneoplastic neurological syndrome in both patients. They received immunomodulatory and cancer treatments without improvement of cerebellar ataxia, even though both were in remission of their cancer (for more than 10 years in one patient). Anti-TRIM9 and anti-TRIM67 Abs were specific to these two patients. All control serum and CSF samples tested were negative for anti-TRIM9 and 67. Anti-TRIM9 and anti-TRIM67 Abs appeared to be specific biomarkers of PCD and should be added to the panel of antigens tested when this is suspected. |
Völz, Ronny; Kim, Soon-Kap; Mi, Jianing; Mariappan, Kiruthiga G; Guo, Xiujie; Bigeard, Jean; Alejandro, Santiago; Pflieger, Delphine; Rayapuram, Naganand; Al-Babili, Salim; Hirt, Heribert The Trihelix transcription factor GT2-like 1 (GTL1) promotes salicylic acid metabolism, and regulates bacterial-triggered immunity Article de journal PLoS genetics, 14 (10), p. e1007708, 2018, ISSN: 1553-7404. @article{volz_trihelix_2018, title = {The Trihelix transcription factor GT2-like 1 (GTL1) promotes salicylic acid metabolism, and regulates bacterial-triggered immunity}, author = {Ronny Völz and Soon-Kap Kim and Jianing Mi and Kiruthiga G Mariappan and Xiujie Guo and Jean Bigeard and Santiago Alejandro and Delphine Pflieger and Naganand Rayapuram and Salim Al-Babili and Heribert Hirt}, doi = {10.1371/journal.pgen.1007708}, issn = {1553-7404}, year = {2018}, date = {2018-10-01}, journal = {PLoS genetics}, volume = {14}, number = {10}, pages = {e1007708}, abstract = {The Trihelix Transcription factor GT2-like 1 (GTL1) was previously shown to be a key regulator of ploidy-dependent trichome growth and drought tolerance. Here, we report that GTL1 plays an important role in coordinating plant immunity. We show that gtl1 mutants are compromised in the regulation of basal immunity, microbial pattern-triggered immunity (PTI) and effector-triggered RIN4-mediated immunity. Transcriptome analysis revealed that GTL1 positively regulates defense genes and inhibits factors that mediate growth and development. By performing hormonal measurements and chromatin-immunoprecipitation studies, we found GTL1 to coordinate genes involved in salicylic acid metabolism, transport and response. Interaction studies and comparative transcriptomics to known data sets revealed that GTL1 is part of the MPK4 pathway and regulates oppositely the expression of differentially expressed genes in mpk4 plants. We introduced the gtl1 mutation in the mpk4 mutant and thereby partially suppressed its dwarfism and the high resistance against a bacterial invader. Our data show that GTL1 is part of the MPK4 pathway and acts as a positive regulator of bacterial-triggered immunity and SA homeostasis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Trihelix Transcription factor GT2-like 1 (GTL1) was previously shown to be a key regulator of ploidy-dependent trichome growth and drought tolerance. Here, we report that GTL1 plays an important role in coordinating plant immunity. We show that gtl1 mutants are compromised in the regulation of basal immunity, microbial pattern-triggered immunity (PTI) and effector-triggered RIN4-mediated immunity. Transcriptome analysis revealed that GTL1 positively regulates defense genes and inhibits factors that mediate growth and development. By performing hormonal measurements and chromatin-immunoprecipitation studies, we found GTL1 to coordinate genes involved in salicylic acid metabolism, transport and response. Interaction studies and comparative transcriptomics to known data sets revealed that GTL1 is part of the MPK4 pathway and regulates oppositely the expression of differentially expressed genes in mpk4 plants. We introduced the gtl1 mutation in the mpk4 mutant and thereby partially suppressed its dwarfism and the high resistance against a bacterial invader. Our data show that GTL1 is part of the MPK4 pathway and acts as a positive regulator of bacterial-triggered immunity and SA homeostasis. |
Gervais, Virginie; Mari, Isabelle Muller Pierre-Olivier; Mourcet, Amandine; Movellan, Kumar Tekwani; Ramos, Pascal; Marcoux, Julien; Guillet, Valérie; Javaid, Sumaira; Burlet-Schiltz, Odile; Czaplicki, Georges; Milon, Alain; Giglia-Mari, Giuseppina Small molecule-based targeting of TTD-A dimerization to control TFIIH transcriptional activity represents a potential strategy for anticancer therapy Article de journal J Biol Chem., 293 (39), p. 14974-14988, 2018. @article{Gervais2018, title = {Small molecule-based targeting of TTD-A dimerization to control TFIIH transcriptional activity represents a potential strategy for anticancer therapy}, author = {Virginie Gervais and Isabelle Muller Pierre-Olivier Mari and Amandine Mourcet and Kumar Tekwani Movellan and Pascal Ramos and Julien Marcoux and Valérie Guillet and Sumaira Javaid and Odile Burlet-Schiltz and Georges Czaplicki and Alain Milon and Giuseppina Giglia-Mari}, doi = {10.1074/jbc.RA118.003444}, year = {2018}, date = {2018-09-28}, journal = {J Biol Chem.}, volume = {293}, number = {39}, pages = {14974-14988}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Shiota, Hitoshi; Barral, Sophie; Buchou, Thierry; Tan, Minjia; Couté, Yohann; Charbonnier, Guillaume; Reynoird, Nicolas; Boussouar, Fayçal; Gérard, Matthieu; Zhu, Mingrui; Bargier, Lisa; Puthier, Denis; Chuffart, Florent; Bourova-Flin, Ekaterina; Picaud, Sarah; Filippakopoulos, Panagis; Goudarzi, Afsaneh; Ibrahim, Ziad; Panne, Daniel; Rousseaux, Sophie; Zhao, Yingming; Khochbin, Saadi Nut Directs p300-Dependent, Genome-Wide Ħ4 Hyperacetylation in Male Germ Cells Article de journal Cell Reports, 24 (13), p. 3477–3487.e6, 2018, ISSN: 2211-1247. @article{shiota_nut_2018, title = {Nut Directs p300-Dependent, Genome-Wide Ħ4 Hyperacetylation in Male Germ Cells}, author = {Hitoshi Shiota and Sophie Barral and Thierry Buchou and Minjia Tan and Yohann Couté and Guillaume Charbonnier and Nicolas Reynoird and Fayçal Boussouar and Matthieu Gérard and Mingrui Zhu and Lisa Bargier and Denis Puthier and Florent Chuffart and Ekaterina Bourova-Flin and Sarah Picaud and Panagis Filippakopoulos and Afsaneh Goudarzi and Ziad Ibrahim and Daniel Panne and Sophie Rousseaux and Yingming Zhao and Saadi Khochbin}, doi = {10.1016/j.celrep.2018.08.069}, issn = {2211-1247}, year = {2018}, date = {2018-09-01}, journal = {Cell Reports}, volume = {24}, number = {13}, pages = {3477--3487.e6}, abstract = {Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome. |
Nguyen, Minh Vu Chuong; Adrait, Annie; Baillet, Athan; Trocmé, Candice; Gottenberg, Jacques-Eric; Gaudin, Philippe Joint, Bone, Spine: Revue Du Rhumatisme, 2018, ISSN: 1778-7254. @article{nguyen_identification_2018, title = {Identification of cartilage oligomeric matrix protein as biomarker predicting abatacept response in rheumatoid arthritis patients with insufficient response to a first anti-TNFα treatment}, author = {Minh Vu Chuong Nguyen and Annie Adrait and Athan Baillet and Candice Trocmé and Jacques-Eric Gottenberg and Philippe Gaudin}, doi = {10.1016/j.jbspin.2018.09.005}, issn = {1778-7254}, year = {2018}, date = {2018-09-01}, journal = {Joint, Bone, Spine: Revue Du Rhumatisme}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Mato, José M; Elortza, Félix; Lu, Shelly C; Brun, Virginie; Paradela, Alberto; Corrales, Fernando J Liver cancer-associated changes to the proteome: what deserves clinical focus? Article de journal Expert Review of Proteomics, 15 (9), p. 749–756, 2018, ISSN: 1744-8387. @article{mato_liver_2018, title = {Liver cancer-associated changes to the proteome: what deserves clinical focus?}, author = {José M Mato and Félix Elortza and Shelly C Lu and Virginie Brun and Alberto Paradela and Fernando J Corrales}, doi = {10.1080/14789450.2018.1521277}, issn = {1744-8387}, year = {2018}, date = {2018-09-01}, journal = {Expert Review of Proteomics}, volume = {15}, number = {9}, pages = {749--756}, abstract = {INTRODUCTION: Hepatocellular carcinoma (HCC) is recognized as the fifth most common neoplasm and currently represents the second leading form of cancer-related death worldwide. Despite great progress has been done in the understanding of its pathogenesis, HCC represents a heavy societal and economic burden as most patients are still diagnosed at advanced stages and the 5-year survival rate remain below 20%. Early detection and revolutionary therapies that rely on the discovery of new molecular biomarkers and therapeutic targets are therefore urgently needed to develop precision medicine strategies for a more efficient management of patients. Areas covered: This review intends to comprehensively analyse the proteomics-based research conducted in the last few years to address some of the principal still open riddles in HCC biology, based on the identification of molecular drivers of tumor progression and metastasis. Expert commentary: The technical advances in mass spectrometry experienced in the last decade have significantly improved the analytical capacity of proteome wide studies. Large-scale protein and protein variant (post-translational modifications) identification and quantification have allowed detailed dissections of molecular mechanisms underlying HCC progression and are already paving the way for the identification of clinically relevant proteins and the development of their use on patient care.}, keywords = {}, pubstate = {published}, tppubtype = {article} } INTRODUCTION: Hepatocellular carcinoma (HCC) is recognized as the fifth most common neoplasm and currently represents the second leading form of cancer-related death worldwide. Despite great progress has been done in the understanding of its pathogenesis, HCC represents a heavy societal and economic burden as most patients are still diagnosed at advanced stages and the 5-year survival rate remain below 20%. Early detection and revolutionary therapies that rely on the discovery of new molecular biomarkers and therapeutic targets are therefore urgently needed to develop precision medicine strategies for a more efficient management of patients. Areas covered: This review intends to comprehensively analyse the proteomics-based research conducted in the last few years to address some of the principal still open riddles in HCC biology, based on the identification of molecular drivers of tumor progression and metastasis. Expert commentary: The technical advances in mass spectrometry experienced in the last decade have significantly improved the analytical capacity of proteome wide studies. Large-scale protein and protein variant (post-translational modifications) identification and quantification have allowed detailed dissections of molecular mechanisms underlying HCC progression and are already paving the way for the identification of clinically relevant proteins and the development of their use on patient care. |
Locard-Paulet, Marie; Parra, Julien; Albigot, Renaud; Mouton-Barbosa, Emmanuelle; Bardi, Laurent; Burlet-Schiltz, Odile; Marcoux, Julien VisioProt-MS: interactive 2D maps from intact protein mass spectrometry Article de journal Bioinformatics, 2018. @article{Locard-Paulet2018, title = {VisioProt-MS: interactive 2D maps from intact protein mass spectrometry}, author = {Marie Locard-Paulet and Julien Parra and Renaud Albigot and Emmanuelle Mouton-Barbosa and Laurent Bardi and Odile Burlet-Schiltz and Julien Marcoux}, doi = {10.1093/bioinformatics/bty680}, year = {2018}, date = {2018-08-06}, journal = {Bioinformatics}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Vinel, Claire; Lukjanenko, Laura; Batut, Aurélie; Deleruyelle, Simon; Pradère, Jean-Philippe; Gonidec, Sophie Le; Dortignac, Alizée; Geoffre, Nancy; Pereira, Ophélie; Karaz, Sonia; Lee, Umji; Camus, Mylène; Chaoui, Karima; Mouisel, Etienne; Bigot, Anne; Mouly, Vincent; Vigneau, Mathieu; Pagano, Allan F; Chopard, Angèle; Pillard, Fabien; Guyonnet, Sophie; Cesari, Matteo; Burlet-Schiltz, Odile; Pahor, Marco; Feige, Jérôme N; Vellas, Bruno; Valet, Philippe; Dray, Cédric The exerkine apelin reverses age-associated sarcopenia Article de journal Nat Med., 24 (9), p. 1360-71, 2018. @article{Vinel2018, title = {The exerkine apelin reverses age-associated sarcopenia}, author = {Claire Vinel and Laura Lukjanenko and Aurélie Batut and Simon Deleruyelle and Jean-Philippe Pradère and Sophie Le Gonidec and Alizée Dortignac and Nancy Geoffre and Ophélie Pereira and Sonia Karaz and Umji Lee and Mylène Camus and Karima Chaoui and Etienne Mouisel and Anne Bigot and Vincent Mouly and Mathieu Vigneau and Allan F. Pagano and Angèle Chopard and Fabien Pillard and Sophie Guyonnet and Matteo Cesari and Odile Burlet-Schiltz and Marco Pahor and Jérôme N. Feige and Bruno Vellas and Philippe Valet and Cédric Dray}, doi = {10.1038/s41591-018-0131-6}, year = {2018}, date = {2018-07-30}, journal = {Nat Med.}, volume = {24}, number = {9}, pages = {1360-71}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Jonik-Nowak, Beata; Menneteau, Thoma; Fesquet, Didier; Baldin, Véronique; Bonne-Andrea, Catherine; Méchali, Francisca; Fabre, Bertrand; Boisguerin, Prisca; de Rossi, Sylvain; Henriquet, Corinne; Pugnière, Martine; Ducoux-Petit, Manuelle; Burlet-Schiltz, Odile; Lamond, Angus I; Fort, Philippe; Boulon, Séverine; Bousquet, Mari-Pierre; Coux, Olivier PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ Article de journal Proc Natl Acad Sci U S A., 115 (28), p. E6477-E6486, 2018. @article{Jonik-Nowak2018, title = {PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ}, author = {Beata Jonik-Nowak and Thoma Menneteau and Didier Fesquet and Véronique Baldin and Catherine Bonne-Andrea and Francisca Méchali and Bertrand Fabre and Prisca Boisguerin and Sylvain de Rossi and Corinne Henriquet and Martine Pugnière and Manuelle Ducoux-Petit and Odile Burlet-Schiltz and Angus I. Lamond and Philippe Fort and Séverine Boulon and Mari-Pierre Bousquet and Olivier Coux}, doi = {10.1073/pnas.1722299115}, year = {2018}, date = {2018-07-10}, journal = {Proc Natl Acad Sci U S A.}, volume = {115}, number = {28}, pages = {E6477-E6486}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Gaud, Guillaume; Roncagalli, Romain; Chaoui, Karima; Bernard, Isabelle; andCéline Colacios, Julien Familiades; Kassem, Sahar; Monsarrat, Bernard; Burlet-Schiltz, Odile; de Peredo, Anne Gonzalez; Malissen, Bernard; Saoudi, Abdelhadi The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4+ T cells Article de journal 11 (538), p. eaar3083, 2018. @article{Gaud2018, title = {The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4+ T cells}, author = {Guillaume Gaud and Romain Roncagalli and Karima Chaoui and Isabelle Bernard and Julien Familiades andCéline Colacios and Sahar Kassem and Bernard Monsarrat and Odile Burlet-Schiltz and Anne Gonzalez de Peredo and Bernard Malissen and Abdelhadi Saoudi}, doi = {10.1126/scisignal.aar3083}, year = {2018}, date = {2018-07-10}, volume = {11}, number = {538}, pages = {eaar3083}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Behrens, Christina; Biela, Inna; andThomas Botzanowski, Stéphanie Petiot-Bécard; Cianférani, Sarah; Sager, Christoph P; Klebe, Gerhard; Heine, Andreas; Reuter, Klaus Homodimer Architecture of QTRT2, the Noncatalytic Subunit of the Eukaryotic tRNA-Guanine Transglycosylase Article de journal Biochemistry, 57 (26), p. 3953–3965, 2018. @article{Behrens2018, title = {Homodimer Architecture of QTRT2, the Noncatalytic Subunit of the Eukaryotic tRNA-Guanine Transglycosylase}, author = {Christina Behrens and Inna Biela and Stéphanie Petiot-Bécard andThomas Botzanowski and Sarah Cianférani and Christoph P. Sager and Gerhard Klebe and Andreas Heine and Klaus Reuter}, doi = {10.1021/acs.biochem.8b00294}, year = {2018}, date = {2018-06-04}, journal = {Biochemistry}, volume = {57}, number = {26}, pages = {3953–3965}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Fröhlich, Tony; Hahn, Friedrich; Belmudes, Lucid; Leidenberger, Maria; Friedrich, Oliver; Kappes, Barbara; Couté, Yohann; Marschall, Manfred; Tsogoeva, Svetlana B Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action Article de journal Chemistry (Weinheim an Der Bergstrasse, Germany), 24 (32), p. 8103–8113, 2018, ISSN: 1521-3765. @article{frohlich_synthesis_2018, title = {Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action}, author = {Tony Fröhlich and Friedrich Hahn and Lucid Belmudes and Maria Leidenberger and Oliver Friedrich and Barbara Kappes and Yohann Couté and Manfred Marschall and Svetlana B Tsogoeva}, doi = {10.1002/chem.201800729}, issn = {1521-3765}, year = {2018}, date = {2018-06-01}, journal = {Chemistry (Weinheim an Der Bergstrasse, Germany)}, volume = {24}, number = {32}, pages = {8103--8113}, abstract = {Generation of dimers, trimers and dendrimers of bioactive compounds is an approach that has recently been developed for the discovery of new potent drug candidates. Herein, we present the synthesis of new artemisinin-derived dimers and dendrimers and investigate their action against malaria parasite Plasmodium falciparum 3D7 strain and human cytomegalovirus (HCMV). Dimer 7 was the most active compound (EC50 1.4 nm) in terms of antimalarial efficacy and was even more effective than the standard drugs dihydroartemisinin (EC50 2.4 nm), artesunic acid (EC50 8.9 nm) and chloroquine (EC50 9.8 nm). Trimer 4 stood out as the most active agent against HCMV in vitro replication and exerted an EC50 value of 0.026 μm, representing an even higher activity than the two reference drugs ganciclovir (EC50 2.60 μm) and artesunic acid (EC50 5.41 μm). In addition, artemisinin-derived dimer 13 and trimer 15 were for the first time both immobilized on TOYOPEARL AF-Amino-650M beads and used for mass spectrometry-based target identification experiments using total lysates of HCMV-infected primary human fibroblasts. Two major groups of novel target candidates, namely cytoskeletal and mitochondrial proteins were obtained. Two putatively compound-binding viral proteins, namely major capsid protein (MCP) and envelope glycoprotein pUL132, which are both essential for HCMV replication, were identified.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Generation of dimers, trimers and dendrimers of bioactive compounds is an approach that has recently been developed for the discovery of new potent drug candidates. Herein, we present the synthesis of new artemisinin-derived dimers and dendrimers and investigate their action against malaria parasite Plasmodium falciparum 3D7 strain and human cytomegalovirus (HCMV). Dimer 7 was the most active compound (EC50 1.4 nm) in terms of antimalarial efficacy and was even more effective than the standard drugs dihydroartemisinin (EC50 2.4 nm), artesunic acid (EC50 8.9 nm) and chloroquine (EC50 9.8 nm). Trimer 4 stood out as the most active agent against HCMV in vitro replication and exerted an EC50 value of 0.026 μm, representing an even higher activity than the two reference drugs ganciclovir (EC50 2.60 μm) and artesunic acid (EC50 5.41 μm). In addition, artemisinin-derived dimer 13 and trimer 15 were for the first time both immobilized on TOYOPEARL AF-Amino-650M beads and used for mass spectrometry-based target identification experiments using total lysates of HCMV-infected primary human fibroblasts. Two major groups of novel target candidates, namely cytoskeletal and mitochondrial proteins were obtained. Two putatively compound-binding viral proteins, namely major capsid protein (MCP) and envelope glycoprotein pUL132, which are both essential for HCMV replication, were identified. |
Jacob, Laurent; Combes, Florence; Burger, Thomas PEPA test: fast and powerful differential analysis from relative quantitative proteomics data using shared peptides Article de journal Biostatistics (Oxford, England), 2018, ISSN: 1468-4357. @article{jacob_pepa_2018, title = {PEPA test: fast and powerful differential analysis from relative quantitative proteomics data using shared peptides}, author = {Laurent Jacob and Florence Combes and Thomas Burger}, doi = {10.1093/biostatistics/kxy021}, issn = {1468-4357}, year = {2018}, date = {2018-06-01}, journal = {Biostatistics (Oxford, England)}, abstract = {We propose a new hypothesis test for the differential abundance of proteins in mass-spectrometry based relative quantification. An important feature of this type of high-throughput analyses is that it involves an enzymatic digestion of the sample proteins into peptides prior to identification and quantification. Due to numerous homology sequences, different proteins can lead to peptides with identical amino acid chains, so that their parent protein is ambiguous. These so-called shared peptides make the protein-level statistical analysis a challenge and are often not accounted for. In this article, we use a linear model describing peptide-protein relationships to build a likelihood ratio test of differential abundance for proteins. We show that the likelihood ratio statistic can be computed in linear time with the number of peptides. We also provide the asymptotic null distribution of a regularized version of our statistic. Experiments on both real and simulated datasets show that our procedures outperforms state-of-the-art methods. The procedures are available via the pepa.test function of the DAPAR Bioconductor R package.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We propose a new hypothesis test for the differential abundance of proteins in mass-spectrometry based relative quantification. An important feature of this type of high-throughput analyses is that it involves an enzymatic digestion of the sample proteins into peptides prior to identification and quantification. Due to numerous homology sequences, different proteins can lead to peptides with identical amino acid chains, so that their parent protein is ambiguous. These so-called shared peptides make the protein-level statistical analysis a challenge and are often not accounted for. In this article, we use a linear model describing peptide-protein relationships to build a likelihood ratio test of differential abundance for proteins. We show that the likelihood ratio statistic can be computed in linear time with the number of peptides. We also provide the asymptotic null distribution of a regularized version of our statistic. Experiments on both real and simulated datasets show that our procedures outperforms state-of-the-art methods. The procedures are available via the pepa.test function of the DAPAR Bioconductor R package. |
Denadai-Souza, Alexandre; Bonnart, Chrystelle; Tapias, Núria Solà; Marcellin, Marlène; andLaurent Alric, Brendan Gilmore; Bonnet, Delphine; Burlet-Schiltz, Odile; Hollenberg, Morley D; Vergnolle, Nathalie; Deraison, Céline Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease Article de journal Sci Rep, 8 (1), p. 7834, 2018. @article{Denadai-Souza2018, title = {Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease}, author = {Alexandre Denadai-Souza and Chrystelle Bonnart and Núria Solà Tapias and Marlène Marcellin and Brendan Gilmore andLaurent Alric and Delphine Bonnet and Odile Burlet-Schiltz and Morley D. Hollenberg and Nathalie Vergnolle and Céline Deraison}, doi = {10.1038/s41598-018-26282-y}, year = {2018}, date = {2018-05-18}, journal = {Sci Rep}, volume = {8}, number = {1}, pages = {7834}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Lefebvre, Cyril; Boulon, Richard; Ducoux, Manuelle; Gavalda, Sabine; Laval, Françoise; Jamet, Stevie; Eynard, Nathalie; Lemassu, Anne; Cam, Kaymeuang; Bousquet, Marie-Pierre; Bardou, Fabienne; Burlet-Schiltz, Odile; Daffé, Mamadou; Quémard, Annaïck HadD, a novel fatty acid synthase type II protein, is essential for alpha- and epoxy-mycolic acid biosynthesis and mycobacterial fitness Article de journal Sci Rep, 8 (1), p. 6034, 2018. @article{Lefebvre2018, title = {HadD, a novel fatty acid synthase type II protein, is essential for alpha- and epoxy-mycolic acid biosynthesis and mycobacterial fitness}, author = {Cyril Lefebvre and Richard Boulon and Manuelle Ducoux and Sabine Gavalda and Françoise Laval and Stevie Jamet and Nathalie Eynard and Anne Lemassu and Kaymeuang Cam and Marie-Pierre Bousquet and Fabienne Bardou and Odile Burlet-Schiltz and Mamadou Daffé and Annaïck Quémard}, doi = {10.1038/s41598-018-24380-5}, year = {2018}, date = {2018-04-16}, journal = {Sci Rep}, volume = {8}, number = {1}, pages = {6034}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Cayrol, Corinne; Duval, Anaïs; Schmitt, Pauline; Roga, Stéphane; Stella, Mylène Camusand Alexandre; Burlet-Schiltz, Odile; Gonzalez de Peredo, Anne ; Girard, Jean-Philippe Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33 Article de journal Nat Immunol, 19 (4), p. 375-385, 2018. @article{Cayrol2018, title = {Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33}, author = {Corinne Cayrol and Anaïs Duval and Pauline Schmitt and Stéphane Roga and Mylène Camusand Alexandre Stella and Odile Burlet-Schiltz and Anne {Gonzalez de Peredo} and Jean-Philippe Girard}, doi = {10.1038/s41590-018-0067-5 }, year = {2018}, date = {2018-03-21}, journal = {Nat Immunol}, volume = {19}, number = {4}, pages = {375-385}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Garcia, Lény; Girod, Marion; Rompais, Magali; Dugourd, Philippe; Carapito, Christine; Lemoine, Jérôme Data-Independent Acquisition Coupled to Visible Laser-Induced Dissociation at 473 nm (DIA-LID) for Peptide-Centric Specific Analysis of Cysteine-Containing Peptide Subset Article de journal Anal Chem., 90 (6), p. 3928-3935, 2018. @article{Garcia2018, title = {Data-Independent Acquisition Coupled to Visible Laser-Induced Dissociation at 473 nm (DIA-LID) for Peptide-Centric Specific Analysis of Cysteine-Containing Peptide Subset}, author = {Lény Garcia and Marion Girod and Magali Rompais and Philippe Dugourd and Christine Carapito and Jérôme Lemoine}, doi = {10.1021/acs.analchem.7b04821}, year = {2018}, date = {2018-03-20}, journal = {Anal Chem.}, volume = {90}, number = {6}, pages = {3928-3935}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Dovgan, I; Erb, S; Hessmann, S; Ursuegui, S; Michel, C; Muller, C; Chaubet, G; Cianférani, S; Wagner, A Arginine-selective bioconjugation with 4-azidophenyl glyoxal: application to the single and dual functionalisation of native antibodies Article de journal Org Biomol Chem., 16 (8), p. 1305-1311, 2018. @article{RN1311, title = {Arginine-selective bioconjugation with 4-azidophenyl glyoxal: application to the single and dual functionalisation of native antibodies}, author = {I Dovgan and S Erb and S Hessmann and S Ursuegui and C Michel and C Muller and G Chaubet and S Cianférani and A Wagner}, doi = {10.1039/c7ob02844j}, year = {2018}, date = {2018-02-21}, journal = {Org Biomol Chem.}, volume = {16}, number = {8}, pages = {1305-1311}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Issa, N; Guillaumot, N; Lauret, E; Matt, N; Schaeffer-Reiss, C; Van Dorsselaer, A; Reichhart, J M; Veillard, F The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway Article de journal Mol Cell, 69 (4), p. 539-550 e6, 2018. @article{RN1312, title = {The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway}, author = {N Issa and N Guillaumot and E Lauret and N Matt and C Schaeffer-Reiss and A {Van Dorsselaer} and J M Reichhart and F Veillard}, doi = {10.1016/j.molcel.2018.01.029}, year = {2018}, date = {2018-02-15}, journal = {Mol Cell}, volume = {69}, number = {4}, pages = {539-550 e6}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Ehkirch, A; D'Atri, V; Rouvière, F; Hernandez-Alba, O; Goyon, A; Colas, O; Sarrut, M; Beck, A; Guillarme, D; Heinisch, S; Cianférani, S An online four-dimensional HICxSEC-IMxMS methodology for proof-of-concept characterization of antibody drug conjugates Article de journal Anal Chem., 90 (3), p. 1578-1586, 2018. @article{RN1307, title = {An online four-dimensional HICxSEC-IMxMS methodology for proof-of-concept characterization of antibody drug conjugates}, author = {A Ehkirch and V D'Atri and F Rouvière and O Hernandez-Alba and A Goyon and O Colas and M Sarrut and A Beck and D Guillarme and S Heinisch and S Cianférani}, doi = {10.1021/acs.analchem.7b02110}, year = {2018}, date = {2018-02-06}, journal = {Anal Chem.}, volume = {90}, number = {3}, pages = {1578-1586}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Lacombe, Maud; Marie-Desvergne, Caroline; Combes, Florence; Kraut, Alexandra; Bruley, Christophe; Vandenbrouck, Yves; Mossuz, Véronique Chamel; Couté, Yohann; Brun, Virginie Proteomic characterization of human exhaled breath condensate Article de journal Journal of Breath Research, 12 (2), p. 021001, 2018, ISSN: 1752-7163. @article{lacombe_proteomic_2018, title = {Proteomic characterization of human exhaled breath condensate}, author = {Maud Lacombe and Caroline Marie-Desvergne and Florence Combes and Alexandra Kraut and Christophe Bruley and Yves Vandenbrouck and Véronique Chamel Mossuz and Yohann Couté and Virginie Brun}, doi = {10.1088/1752-7163/aa9e71}, issn = {1752-7163}, year = {2018}, date = {2018-02-01}, journal = {Journal of Breath Research}, volume = {12}, number = {2}, pages = {021001}, abstract = {To improve biomedical knowledge and to support biomarker discovery studies, it is essential to establish comprehensive proteome maps for human tissues and biofluids, and to make them publicly accessible. In this study, we performed an in-depth proteomics characterization of exhaled breath condensate (EBC), a sample obtained non-invasively by condensation of exhaled air that contains submicron droplets of airway lining fluid. Two pooled samples of EBC, each obtained from 10 healthy donors, were processed using a straightforward protocol based on sample lyophilization, in-gel digestion and liquid chromatography tandem-mass spectrometry analysis. Two 'technical' control samples were processed in parallel to the pooled samples to correct for exogenous protein contamination. A total of 229 unique proteins were identified in EBC among which 153 proteins were detected in both EBC pooled samples. A detailed bioinformatics analysis of these 153 proteins showed that most of the proteins identified corresponded to proteins secreted in the respiratory tract (lung, bronchi). Eight proteins were salivary proteins. Our dataset is described and has been made accessible through the ProteomeXchange database (dataset identifier: PXD007591) and is expected to be useful for future MS-based biomarker studies using EBC as the diagnostic specimen.}, keywords = {}, pubstate = {published}, tppubtype = {article} } To improve biomedical knowledge and to support biomarker discovery studies, it is essential to establish comprehensive proteome maps for human tissues and biofluids, and to make them publicly accessible. In this study, we performed an in-depth proteomics characterization of exhaled breath condensate (EBC), a sample obtained non-invasively by condensation of exhaled air that contains submicron droplets of airway lining fluid. Two pooled samples of EBC, each obtained from 10 healthy donors, were processed using a straightforward protocol based on sample lyophilization, in-gel digestion and liquid chromatography tandem-mass spectrometry analysis. Two 'technical' control samples were processed in parallel to the pooled samples to correct for exogenous protein contamination. A total of 229 unique proteins were identified in EBC among which 153 proteins were detected in both EBC pooled samples. A detailed bioinformatics analysis of these 153 proteins showed that most of the proteins identified corresponded to proteins secreted in the respiratory tract (lung, bronchi). Eight proteins were salivary proteins. Our dataset is described and has been made accessible through the ProteomeXchange database (dataset identifier: PXD007591) and is expected to be useful for future MS-based biomarker studies using EBC as the diagnostic specimen. |
Grzela, R; Nusbaum, J; Fieulaine, S; Lavecchia, F; Desmadril, M; Nhiri, N; Van Dorsselaer, A; Cianférani, S; Jacquet, E; Meinnel, T; Giglione, C Peptide deformylases from Vibrio parahaemolyticus phage and bacteria display similar deformylase activity and inhibitor binding clefts Article de journal Biochim Biophys Acta., 1866 (2), p. 348-355, 2018. @article{RN1310, title = {Peptide deformylases from Vibrio parahaemolyticus phage and bacteria display similar deformylase activity and inhibitor binding clefts}, author = {R Grzela and J Nusbaum and S Fieulaine and F Lavecchia and M Desmadril and N Nhiri and A {Van Dorsselaer} and S Cianférani and E Jacquet and T Meinnel and C Giglione}, doi = {10.1016/j.bbapap.2017.10.007}, year = {2018}, date = {2018-02-01}, journal = {Biochim Biophys Acta.}, volume = {1866}, number = {2}, pages = {348-355}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
A, Métais; I, Lamsoul; A, Melet; S, Uttenweiler-Joseph; R, Poincloux; S, Stefanovic; A, Valière; de A, Gonzalez Peredo; A, Stella; O, Burlet-Schiltz; S, Zaffran; PG, Lutz; C, Moog-Lutz Asb2α-Filamin A Axis Is Essential for Actin Cytoskeleton Remodeling During Heart Development Article de journal Circ Res., 122 (6), p. 34-48, 2018. @article{A2018, title = {Asb2α-Filamin A Axis Is Essential for Actin Cytoskeleton Remodeling During Heart Development}, author = {Métais A and Lamsoul I and Melet A and Uttenweiler-Joseph S and Poincloux R and Stefanovic S and Valière A and Gonzalez de Peredo A and Stella A and Burlet-Schiltz O and Zaffran S and Lutz PG and Moog-Lutz C}, doi = {10.1161/CIRCRESAHA.117.312015}, year = {2018}, date = {2018-01-26}, journal = {Circ Res.}, volume = {122}, number = {6}, pages = {34-48}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Mori, M; Kovalenko, L; Malancona, S; Saladini, F; Forni, De D; Pires, M; Humbert, N; Real, E; Botzanowski, T; Cianférani, S; Giannini, A; Lang, MC. Dasso; Cugia, G; Poddesu, B; Lori, F; Zazzi, M; Harper, S; Summa, V; Mely, Y; Botta, M Structure-Based Identification of HIV-1 Nucleocapsid Protein Inhibitors Active against Wild-Type and Drug-Resistant HIV-1 Strains Article de journal ACS Chem Biol., 13 (1), p. 253-266, 2018. @article{RN1308, title = {Structure-Based Identification of HIV-1 Nucleocapsid Protein Inhibitors Active against Wild-Type and Drug-Resistant HIV-1 Strains}, author = {M Mori and L Kovalenko and S Malancona and F Saladini and D De Forni and M Pires and N Humbert and E Real and T Botzanowski and S Cianférani and A Giannini and MC. Dasso Lang and G Cugia and B Poddesu and F Lori and M Zazzi and S Harper and V Summa and Y Mely and M Botta}, doi = {10.1021/acschembio.7b00907}, year = {2018}, date = {2018-01-19}, journal = {ACS Chem Biol.}, volume = {13}, number = {1}, pages = {253-266}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Husson, G; Delangle, A; O'Hara, J; Cianférani, S; Gervais, A; Van Dorsselaer, A; Bracewell, D; Carapito, C Dual Data-Independent Acquisition Approach Combining Global HCP Profiling and Absolute Quantification of Key Impurities during Bioprocess Development Article de journal Anal Chem., 90 (2), p. 1241-1247, 2018. @article{RN1306, title = {Dual Data-Independent Acquisition Approach Combining Global HCP Profiling and Absolute Quantification of Key Impurities during Bioprocess Development}, author = {G Husson and A Delangle and J O'Hara and S Cianférani and A Gervais and A {Van Dorsselaer} and D Bracewell and C Carapito}, doi = {10.1021/acs.analchem.7b03965 }, year = {2018}, date = {2018-01-16}, journal = {Anal Chem.}, volume = {90}, number = {2}, pages = {1241-1247}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
L, Favre; A, Ortalo-Magné; C, Pichereaux; A, Gargaros; O, Burlet-Schiltz; V, Cotelle; G., Culioli Metabolome and proteome changes between biofilm and planktonic phenotypes of the marine bacterium Pseudoalteromonas lipolytica TC8 Article de journal Biofouling, 34 (2), p. 132-148, 2018. @article{L2018, title = {Metabolome and proteome changes between biofilm and planktonic phenotypes of the marine bacterium Pseudoalteromonas lipolytica TC8}, author = {Favre L and Ortalo-Magné A and Pichereaux C and Gargaros A and Burlet-Schiltz O and Cotelle V and Culioli G.}, doi = {10.1080/08927014.2017.1413551}, year = {2018}, date = {2018-01-10}, journal = {Biofouling}, volume = {34}, number = {2}, pages = {132-148}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Rayapuram, Naganand; Bigeard, Jean; Alhoraibi, Hanna; Bonhomme, Ludovic; Hesse, Anne-Marie; Vinh, Joëlle; Hirt, Heribert; Pflieger, Delphine Quantitative Phosphoproteomic Analysis Reveals Shared and Specific Targets ofArabidopsisMitogen-Activated Protein Kinases (MAPKs) MPK3, MPK4, and MPK6 Article de journal Molecular & cellular proteomics: MCP, 17 (1), p. 61–80, 2018, ISSN: 1535-9484. @article{rayapuram_quantitative_2018, title = {Quantitative Phosphoproteomic Analysis Reveals Shared and Specific Targets ofArabidopsisMitogen-Activated Protein Kinases (MAPKs) MPK3, MPK4, and MPK6}, author = {Naganand Rayapuram and Jean Bigeard and Hanna Alhoraibi and Ludovic Bonhomme and Anne-Marie Hesse and Joëlle Vinh and Heribert Hirt and Delphine Pflieger}, doi = {10.1074/mcp.RA117.000135}, issn = {1535-9484}, year = {2018}, date = {2018-01-01}, journal = {Molecular & cellular proteomics: MCP}, volume = {17}, number = {1}, pages = {61--80}, abstract = {In Arabidopsis, mitogen-activated protein kinases MPK3, MPK4, and MPK6 constitute essential relays for a variety of functions including cell division, development and innate immunity. Although some substrates of MPK3, MPK4 and MPK6 have been identified, the picture is still far from complete. To identify substrates of these MAPKs likely involved in cell division, growth and development we compared the phosphoproteomes of wild-type andmpk3,mpk4, andmpk6.To study the function of these MAPKs in innate immunity, we analyzed their phosphoproteomes following microbe-associated molecular pattern (MAMP) treatment. Partially overlapping substrates were retrieved for all three MAPKs, showing target specificity to one, two or all three MAPKs in different biological processes. More precisely, our results illustrate the fact that the entity to be defined as a specific or a shared substrate for MAPKs is not a phosphoprotein but a particular (S/T)P phosphorylation site in a given protein. One hundred fifty-two peptides were identified to be differentially phosphorylated in response to MAMP treatment and/or when compared between genotypes and 70 of them could be classified as putative MAPK targets. Biochemical analysis of a number of putative MAPK substrates by phosphorylation and interaction assays confirmed the global phosphoproteome approach. Our study also expands the set of MAPK substrates to involve other protein kinases, including calcium-dependent (CDPK) and sugar nonfermenting (SnRK) protein kinases.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In Arabidopsis, mitogen-activated protein kinases MPK3, MPK4, and MPK6 constitute essential relays for a variety of functions including cell division, development and innate immunity. Although some substrates of MPK3, MPK4 and MPK6 have been identified, the picture is still far from complete. To identify substrates of these MAPKs likely involved in cell division, growth and development we compared the phosphoproteomes of wild-type andmpk3,mpk4, andmpk6.To study the function of these MAPKs in innate immunity, we analyzed their phosphoproteomes following microbe-associated molecular pattern (MAMP) treatment. Partially overlapping substrates were retrieved for all three MAPKs, showing target specificity to one, two or all three MAPKs in different biological processes. More precisely, our results illustrate the fact that the entity to be defined as a specific or a shared substrate for MAPKs is not a phosphoprotein but a particular (S/T)P phosphorylation site in a given protein. One hundred fifty-two peptides were identified to be differentially phosphorylated in response to MAMP treatment and/or when compared between genotypes and 70 of them could be classified as putative MAPK targets. Biochemical analysis of a number of putative MAPK substrates by phosphorylation and interaction assays confirmed the global phosphoproteome approach. Our study also expands the set of MAPK substrates to involve other protein kinases, including calcium-dependent (CDPK) and sugar nonfermenting (SnRK) protein kinases. |
Burger, Thomas Gentle Introduction to the Statistical Foundations of False Discovery Rate in Quantitative Proteomics Article de journal Journal of Proteome Research, 17 (1), p. 12–22, 2018, ISSN: 1535-3907. @article{burger_gentle_2018, title = {Gentle Introduction to the Statistical Foundations of False Discovery Rate in Quantitative Proteomics}, author = {Thomas Burger}, doi = {10.1021/acs.jproteome.7b00170}, issn = {1535-3907}, year = {2018}, date = {2018-01-01}, journal = {Journal of Proteome Research}, volume = {17}, number = {1}, pages = {12--22}, abstract = {The vocabulary of theoretical statistics can be difficult to embrace from the viewpoint of computational proteomics research, even though the notions it conveys are essential to publication guidelines. For example, "adjusted p-values", "q-values", and "false discovery rates" are essentially similar concepts, whereas "false discovery rate" and "false discovery proportion" must not be confused, even though "rate" and "proportion" are related in everyday language. In the interdisciplinary context of proteomics, such subtleties may cause misunderstandings. This article aims to provide an easy-to-understand explanation of these four notions (and a few other related ones). Their statistical foundations are dealt with from a perspective that largely relies on intuition, addressing mainly protein quantification but also, to some extent, peptide identification. In addition, a clear distinction is made between concepts that define an individual property (i.e., related to a peptide or a protein) and those that define a set property (i.e., related to a list of peptides or proteins).}, keywords = {}, pubstate = {published}, tppubtype = {article} } The vocabulary of theoretical statistics can be difficult to embrace from the viewpoint of computational proteomics research, even though the notions it conveys are essential to publication guidelines. For example, "adjusted p-values", "q-values", and "false discovery rates" are essentially similar concepts, whereas "false discovery rate" and "false discovery proportion" must not be confused, even though "rate" and "proportion" are related in everyday language. In the interdisciplinary context of proteomics, such subtleties may cause misunderstandings. This article aims to provide an easy-to-understand explanation of these four notions (and a few other related ones). Their statistical foundations are dealt with from a perspective that largely relies on intuition, addressing mainly protein quantification but also, to some extent, peptide identification. In addition, a clear distinction is made between concepts that define an individual property (i.e., related to a peptide or a protein) and those that define a set property (i.e., related to a list of peptides or proteins). |
Kennani, Sara El; Crespo, Marion; Govin, Jérôme; Pflieger, Delphine Proteomic Analysis of Histone Variants and Their PTMs: Strategies and Pitfalls Article de journal Proteomes, 6 (3), 2018, ISSN: 2227-7382. @article{el_kennani_proteomic_2018, title = {Proteomic Analysis of Histone Variants and Their PTMs: Strategies and Pitfalls}, author = {Sara El Kennani and Marion Crespo and Jérôme Govin and Delphine Pflieger}, doi = {10.3390/proteomes6030029}, issn = {2227-7382}, year = {2018}, date = {2018-01-01}, journal = {Proteomes}, volume = {6}, number = {3}, abstract = {Epigenetic modifications contribute to the determination of cell fate and differentiation. The molecular mechanisms underlying histone variants and post-translational modifications (PTMs) have been studied in the contexts of development, differentiation, and disease. Antibody-based assays have classically been used to target PTMs, but these approaches fail to reveal combinatorial patterns of modifications. In addition, some histone variants are so similar to canonical histones that antibodies have difficulty distinguishing between these isoforms. Mass spectrometry (MS) has progressively developed as a powerful technology for the study of histone variants and their PTMs. Indeed, MS analyses highlighted exquisitely complex combinations of PTMs, suggesting “crosstalk” between them, and also revealed that PTM patterns are often variant-specific. Even though the sensitivity and acquisition speed of MS instruments have considerably increased alongside the development of computational tools for the study of multiple PTMs, it remains challenging to correctly describe the landscape of histone PTMs, and in particular to confidently assign modifications to specific amino acids. Here, we provide an inventory of MS-based strategies and of the pitfalls inherent to histone PTM and variant characterization, while stressing the complex interplay between PTMs and histone sequence variations. We will particularly illustrate the roles played by MS-based analyses in identifying and quantifying histone variants and modifications.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Epigenetic modifications contribute to the determination of cell fate and differentiation. The molecular mechanisms underlying histone variants and post-translational modifications (PTMs) have been studied in the contexts of development, differentiation, and disease. Antibody-based assays have classically been used to target PTMs, but these approaches fail to reveal combinatorial patterns of modifications. In addition, some histone variants are so similar to canonical histones that antibodies have difficulty distinguishing between these isoforms. Mass spectrometry (MS) has progressively developed as a powerful technology for the study of histone variants and their PTMs. Indeed, MS analyses highlighted exquisitely complex combinations of PTMs, suggesting “crosstalk” between them, and also revealed that PTM patterns are often variant-specific. Even though the sensitivity and acquisition speed of MS instruments have considerably increased alongside the development of computational tools for the study of multiple PTMs, it remains challenging to correctly describe the landscape of histone PTMs, and in particular to confidently assign modifications to specific amino acids. Here, we provide an inventory of MS-based strategies and of the pitfalls inherent to histone PTM and variant characterization, while stressing the complex interplay between PTMs and histone sequence variations. We will particularly illustrate the roles played by MS-based analyses in identifying and quantifying histone variants and modifications. |
Kennani, Sara El; Adrait, Annie; Permiakova, Olga; Hesse, Anne-Marie; Ialy-Radio, Côme; Ferro, Myriam; Brun, Virginie; Cocquet, Julie; Govin, Jérôme; Pflieger, Delphine Systematic quantitative analysis of Ħ2A and Ħ2B variants by targeted proteomics Article de journal Epigenetics & Chromatin, 11 (1), p. 2, 2018, ISSN: 1756-8935. @article{el_kennani_systematic_2018, title = {Systematic quantitative analysis of Ħ2A and Ħ2B variants by targeted proteomics}, author = {Sara El Kennani and Annie Adrait and Olga Permiakova and Anne-Marie Hesse and Côme Ialy-Radio and Myriam Ferro and Virginie Brun and Julie Cocquet and Jérôme Govin and Delphine Pflieger}, doi = {10.1186/s13072-017-0172-y}, issn = {1756-8935}, year = {2018}, date = {2018-01-01}, journal = {Epigenetics & Chromatin}, volume = {11}, number = {1}, pages = {2}, abstract = {BACKGROUND: Histones organize DNA into chromatin through a variety of processes. Among them, a vast diversity of histone variants can be incorporated into chromatin and finely modulate its organization and functionality. Classically, the study of histone variants has largely relied on antibody-based assays. However, antibodies have a limited efficiency to discriminate between highly similar histone variants. RESULTS: In this study, we established a mass spectrometry-based analysis to address this challenge. We developed a targeted proteomics method, using selected reaction monitoring or parallel reaction monitoring, to quantify a maximum number of histone variants in a single multiplexed assay, even when histones are present in a crude extract. This strategy was developed on H2A and H2B variants, using 55 peptides corresponding to 25 different histone sequences, among which a few differ by a single amino acid. The methodology was then applied to mouse testis extracts in which almost all histone variants are expressed. It confirmed the abundance profiles of several testis-specific histones during successive stages of spermatogenesis and the existence of predicted H2A.L.1 isoforms. This methodology was also used to explore the over-expression pattern of H2A.L.1 isoforms in a mouse model of male infertility. CONCLUSIONS: Our results demonstrate that targeted proteomics is a powerful method to quantify highly similar histone variants and isoforms. The developed method can be easily transposed to the study of human histone variants, whose abundance can be deregulated in various diseases.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Histones organize DNA into chromatin through a variety of processes. Among them, a vast diversity of histone variants can be incorporated into chromatin and finely modulate its organization and functionality. Classically, the study of histone variants has largely relied on antibody-based assays. However, antibodies have a limited efficiency to discriminate between highly similar histone variants. RESULTS: In this study, we established a mass spectrometry-based analysis to address this challenge. We developed a targeted proteomics method, using selected reaction monitoring or parallel reaction monitoring, to quantify a maximum number of histone variants in a single multiplexed assay, even when histones are present in a crude extract. This strategy was developed on H2A and H2B variants, using 55 peptides corresponding to 25 different histone sequences, among which a few differ by a single amino acid. The methodology was then applied to mouse testis extracts in which almost all histone variants are expressed. It confirmed the abundance profiles of several testis-specific histones during successive stages of spermatogenesis and the existence of predicted H2A.L.1 isoforms. This methodology was also used to explore the over-expression pattern of H2A.L.1 isoforms in a mouse model of male infertility. CONCLUSIONS: Our results demonstrate that targeted proteomics is a powerful method to quantify highly similar histone variants and isoforms. The developed method can be easily transposed to the study of human histone variants, whose abundance can be deregulated in various diseases. |
