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2. Nanotopography by chromatic confocal microscopy of the endothelium in Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy and healthy corneas.

Author

Vaitinadapoulé, Hanielle, Poinard, Sylvain, Zhiguo He, Pascale-Hamri, Alina, Thomas, Justin, Gain, Philippe, Thuret, Jean-Yves, Mascarelli, Frédéric, and Thuret, Gilles

Abstract

Aim To investigate the interest of chromatic confocal microscopy (CCM) to characterise guttae in Fuchs endothelial corneal dystrophy (FECD). Methods Descemet's membranes (DM) were obtained during endothelial keratoplasty in patients with FECD and pseudophakic bullous keratopathy (PBK). They were compared with healthy samples obtained from body donation to science. Samples were fixed in 0.5% paraformaldehyde and flat mounted. Surface roughness of DMs was quantified using CCM and the AltiMap software that provided the maximum peak (Sp) and valley (Sv) heights, the mean square roughness (Rq) and the asymmetry coefficient (Ssk). Results The physiological roughness of healthy samples was characterised by an Rq of 0.12±0.05 µm, which was two times rougher than in PBK (Rq=0.06±0.03 µm), but both were still flat with a symmetrical distribution between peaks and valleys (Ssk close to 0, npeaks=nvalleys), smaller than 1 µm. In FECD, the maximum peak height was 5.10±2.40 µm, up to 5.8 and 8.3 times higher than the control and PBK, respectively. The maximum valley depth was half than the peak (2.28±0.89 µm). The surface with guttae was very rough (Rq=0.45±0.14 µm) and the Ssk=1.84± 0.43 µm, greater than 0, confirms an asymmetric surface with high peaks and low valleys (npeaks>nvalleys). Moreover, the CCM provided quantitative parameters allowing to distinguish different types of guttae from different patients. Conclusions CCM is an innovative approach to describe and quantify different morphologies of guttae. It could be useful to analyse the different stages of FECD and define subgroups of patients. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1

Author

Bakail, May, Gaubert, Albane, Andreani, Jessica, Moal, Gwenaëlle, Pinna, Guillaume, Boyarchuk, Ekaterina, Gaillard, Marie-Cécile, Courbeyrette, Regis, Mann, Carl, Thuret, Jean-Yves, Guichard, Bérengère, Murciano, Brice, Richet, Nicolas, Poitou, Adeline, Frederic, Claire, Le Du, Marie-Hélène, Agez, Morgane, Roelants, Caroline, Gurard-Levin, Zachary A., Almouzni, Geneviève, Cherradi, Nadia, Guerois, Raphael, and Ochsenbein, Françoise

Published
2019
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9. The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19

Author

Armengaud, Jean [0000-0003-1589-445X], Thuret, Jean-Yves [0000-0001-5385-7620], Anken, Eelco van [0000-0001-9529-2701], Acosta-Alvear, Diego [0000-0002-1139-8486], Aragón, Tomás [0000-0002-1700-2729], Arias, Carolina [0000-0002-4445-0826], Blondel, Marc [0000-0003-4897-2995], Braakman, Ineke [0000-0003-1592-4364], Collet, Jean-François [0000-0001-8069-7036], Courcol, René [0000-0003-2324-5687], Danchin, Antoine [0000-0002-6350-5001], Deleuze, Jean-François [0000-0002-5358-4463], Lavigne, Jean-Philippe [0000-0002-9484-0304], Lucas, Sophie [0000-0003-1287-7996], Michiels, Thomas [0000-0001-9615-8053], Moore, Edward R.B. [0000-0001-7693-924X], Nixon-Abell, Jonathon [0000-0003-4169-0012], Rosselló-Mora, Ramón [0000-0001-8253-3107], Shi, Zheng-Li [0000-0001-8089-163X], Siccardi, Antonio G. [0000-0002-1654-5545], Sitia, Roberto [0000-0001-7086-4152], Tillett, Daniel [0000-0003-1061-0489], Timmis, Kenneth N. [0000-0002-0066-4670], Toledano, Michel B. [0000-0002-3079-1179], Sluijs, Peter van der [0000-0002-4485-3342], Vicenzi, Elisa [0000-0003-0051-3968], Armengaud, Jean, Delaunay, Agnes, Thuret, Jean-Yves, Anken, Eelco van, Acosta-Alvear, Diego, Aragón, Tomás, Arias, Carolina, Blondel, Marc, Braakman, Ineke, Collet, Jean-François, Courcol, René, Danchin, Antoine, Deleuze, Jean-François, Lavigne, Jean-Philippe, Lucas, Sophie, Michiels, Thomas, Moore, Edward R.B., Nixon-Abell, Jonathon, Rosselló-Mora, Ramón, Shi, Zheng-Li, Siccardi, Antonio G., Sitia, Roberto, Tillett, Daniel, Timmis, Kenneth N., Toledano, Michel B., Sluijs, Peter van der, Vicenzi, Elisa, Armengaud, Jean [0000-0003-1589-445X], Thuret, Jean-Yves [0000-0001-5385-7620], Anken, Eelco van [0000-0001-9529-2701], Acosta-Alvear, Diego [0000-0002-1139-8486], Aragón, Tomás [0000-0002-1700-2729], Arias, Carolina [0000-0002-4445-0826], Blondel, Marc [0000-0003-4897-2995], Braakman, Ineke [0000-0003-1592-4364], Collet, Jean-François [0000-0001-8069-7036], Courcol, René [0000-0003-2324-5687], Danchin, Antoine [0000-0002-6350-5001], Deleuze, Jean-François [0000-0002-5358-4463], Lavigne, Jean-Philippe [0000-0002-9484-0304], Lucas, Sophie [0000-0003-1287-7996], Michiels, Thomas [0000-0001-9615-8053], Moore, Edward R.B. [0000-0001-7693-924X], Nixon-Abell, Jonathon [0000-0003-4169-0012], Rosselló-Mora, Ramón [0000-0001-8253-3107], Shi, Zheng-Li [0000-0001-8089-163X], Siccardi, Antonio G. [0000-0002-1654-5545], Sitia, Roberto [0000-0001-7086-4152], Tillett, Daniel [0000-0003-1061-0489], Timmis, Kenneth N. [0000-0002-0066-4670], Toledano, Michel B. [0000-0002-3079-1179], Sluijs, Peter van der [0000-0002-4485-3342], Vicenzi, Elisa [0000-0003-0051-3968], Armengaud, Jean, Delaunay, Agnes, Thuret, Jean-Yves, Anken, Eelco van, Acosta-Alvear, Diego, Aragón, Tomás, Arias, Carolina, Blondel, Marc, Braakman, Ineke, Collet, Jean-François, Courcol, René, Danchin, Antoine, Deleuze, Jean-François, Lavigne, Jean-Philippe, Lucas, Sophie, Michiels, Thomas, Moore, Edward R.B., Nixon-Abell, Jonathon, Rosselló-Mora, Ramón, Shi, Zheng-Li, Siccardi, Antonio G., Sitia, Roberto, Tillett, Daniel, Timmis, Kenneth N., Toledano, Michel B., Sluijs, Peter van der, and Vicenzi, Elisa

Abstract

The current SARS‐CoV‐2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID‐19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS‐CoV‐2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS‐CoV‐2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS‐CoV‐2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state‐of‐the‐art nucleic acid sequencing technologies, we can follow in detail how SARS‐CoV‐2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS‐CoV‐2 variants across the globe should be of key interest in our fight against the pandemic.

Published
2020

10. The importance of naturally attenuated SARS‐CoV ‐2 in the fight against COVID ‐19

Author

Armengaud, Jean, Delaunay‐Moisan, Agnès, Thuret, Jean‐Yves, Anken, Eelco, Acosta‐Alvear, Diego, Aragón, Tomás, Arias, Carolina, Blondel, Marc, Braakman, Ineke, Collet, Jean‐François, Courcol, René, Danchin, Antoine, Deleuze, Jean‐François, Lavigne, Jean‐Philippe, Lucas, Sophie, Michiels, Thomas, Moore, Edward R. B., Nixon‐Abell, Jonathon, Rossello‐Mora, Ramon, Shi, Zheng‐Li, Siccardi, Antonio G., Sitia, Roberto, Tillett, Daniel, Timmis, Kenneth N., Toledano, Michel B., Sluijs, Peter, Vicenzi, Elisa, Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Stress Oxydatif et Cancer (SOC), Département Biologie Cellulaire (BioCell), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Sénescence et stabilité génomique (SEN), Département Biologie des Génomes (DBG), San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, University of California [Santa Barbara] (UC Santa Barbara), University of California (UC), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Utrecht University [Utrecht], Université Catholique de Louvain = Catholic University of Louvain (UCL), Walloon Excellence in Life sciences and BIOtechnology [Liège] (WELBIO), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Gothenburg (GU), Sahlgrenska University Hospital [Gothenburg], University of Cambridge [UK] (CAM), Institut Mediterrani d'Estudis Avancats (IMEDEA), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad de las Islas Baleares (UIB), Wuhan Institute of Virology [Wuhan, China], Chinese Academy of Sciences [Wuhan Branch], Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig], ANR-17-CE18-0023,Phylopeptidomics,Identification rapide de bactéries pathogènes et résistances aux antibiotiques(2017), Armengaud, Jean [0000-0003-1589-445X], Thuret, Jean-Yves [0000-0001-5385-7620], Anken, Eelco van [0000-0001-9529-2701], Acosta-Alvear, Diego [0000-0002-1139-8486], Aragón, Tomás [0000-0002-1700-2729], Arias, Carolina [0000-0002-4445-0826], Blondel, Marc [0000-0003-4897-2995], Braakman, Ineke [0000-0003-1592-4364], Collet, Jean-François [0000-0001-8069-7036], Courcol, René [0000-0003-2324-5687], Danchin, Antoine [0000-0002-6350-5001], Deleuze, Jean-François [0000-0002-5358-4463], Lavigne, Jean-Philippe [0000-0002-9484-0304], Lucas, Sophie [0000-0003-1287-7996], Michiels, Thomas [0000-0001-9615-8053], Moore, Edward R.B. [0000-0001-7693-924X], Nixon-Abell, Jonathon [0000-0003-4169-0012], Rosselló-Mora, Ramón [0000-0001-8253-3107], Shi, Zheng-Li [0000-0001-8089-163X], Siccardi, Antonio G. [0000-0002-1654-5545], Sitia, Roberto [0000-0001-7086-4152], Tillett, Daniel [0000-0003-1061-0489], Timmis, Kenneth N. [0000-0002-0066-4670], Toledano, Michel B. [0000-0002-3079-1179], Sluijs, Peter van der [0000-0002-4485-3342], Vicenzi, Elisa [0000-0003-0051-3968], University of California [Santa Barbara] (UCSB), University of California, Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Technical University Braunschweig, Armengaud, Jean, Thuret, Jean-Yves, Anken, Eelco van, Acosta-Alvear, Diego, Aragón, Tomás, Arias, Carolina, Blondel, Marc, Braakman, Ineke, Collet, Jean-François, Courcol, René, Danchin, Antoine, Deleuze, Jean-François, Lavigne, Jean-Philippe, Lucas, Sophie, Michiels, Thomas, Moore, Edward R.B., Nixon-Abell, Jonathon, Rosselló-Mora, Ramón, Shi, Zheng-Li, Siccardi, Antonio G., Sitia, Roberto, Tillett, Daniel, Timmis, Kenneth N., Toledano, Michel B., Sluijs, Peter van der, Vicenzi, Elisa, Armengaud, J., Delaunay-Moisan, A., Thuret, J. -Y., van Anken, E., Acosta-Alvear, D., Aragon, T., Arias, C., Blondel, M., Braakman, I., Collet, J. -F., Courcol, R., Danchin, A., Deleuze, J. -F., Lavigne, J. -P., Lucas, S., Michiels, T., Moore, E. R. B., Nixon-Abell, J., Rossello-Mora, R., Shi, Z., Siccardi, A. G., Sitia, R., Tillett, D., Timmis, K. N., Toledano, M. B., van der Sluijs, P., Vicenzi, E., and UCL - SSS/DDUV - Institut de Duve

Subjects
Opinion, viruses, Pneumonia, Viral, Gene Expression, Microbiology, Disease Outbreaks, Evolution, Molecular, Betacoronavirus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, Health emergency, Selection, Genetic, Pandemics, Ecology, Evolution, Behavior and Systematics, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Virulence, SARS-CoV-2, fungi, COVID-19, SARS Virus, Adaptation, Physiological, Severe acute respiratory syndrome-related coronavirus, Host-Pathogen Interactions, Mutation, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Coronavirus Infections
Abstract

The current SARS‐CoV‐2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID‐19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS‐CoV‐2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS‐CoV‐2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS‐CoV‐2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state‐of‐the‐art nucleic acid sequencing technologies, we can follow in detail how SARS‐CoV‐2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS‐CoV‐2 variants across the globe should be of key interest in our fight against the pandemic.

Published
2020
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13. Histone Variant H2A.J Is Enriched in Luminal Epithelial Gland Cells

Author

Redon, Christophe E., primary, Schmal, Zoe, additional, Tewary, Gargi, additional, Mangelinck, Adèle, additional, Courbeyrette, Régis, additional, Thuret, Jean-Yves, additional, Aladjem, Mirit I., additional, Bonner, William M., additional, Rübe, Claudia E., additional, and Mann, Carl, additional

Published
2021
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18. Conception sur une base rationnelle de peptides de haute affinité inhibant l'histone chaperon ASF1

Author

Bakail, May, Gaubert, Albane, Andreani, Jessica, Moal, Gwenaëlle, Pinna, Guillaume, Boyarchuk, Ekaterina, Gaillard, Marie-Cécile, Courbeyrette, Régis, Mann, Carl, Thuret, Jean-Yves, Guichard, Berengère, Murciano, Brice, Richet, Nicolas, Poitou, Adeline, Frederic, Claire, Le Du, Marie-Hélène, Agez, Morgane, Roelants, Caroline, Gurard-Levin, Zachary, Almouzni, Geneviève, Cherradi, Nadia, Guérois, Raphaël, Ochsenbein, Françoise, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Assemblage moléculaire et intégrité du génome (AMIG), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Structurale et Radiobiologie (LBSR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), PARi (PARI), Département Plateforme (PF I2BC), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Sénescence et stabilité génomique (SEN), Département Biologie des Génomes (DBG), Vaccination Antiparasitaire : Laboratoire de Biologie Cellulaire et Moléculaire (LBCM), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Enveloppe Nucléaire, Télomères et Réparation de l’ADN (INTGEN), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Invasion mechanisms in angiogenesis and cancer (IMAC), Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique du noyau [Institut Curie], and Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Rosetta Design, Drug Design, [SDV]Life Sciences [q-bio], X-Ray Crystallography, Peptide Inhibitor, Epigenetics, MESH: Amino Acid Sequence, Binding Sites, Histones / metabolism, Neoplasms / drug therapy, Transplantation, Homologous, Cell Penetrating Peptide, Chromatin, Protein-Protein Interaction, Protein Binding, Cancer, [SHS]Humanities and Social Sciences
Abstract

International audience; Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy.; La fonction anti-silencing 1 (ASF1) est un chaperon d'histone H3-H4 conservé, impliqué dans la dynamique des histones pendant la réplication, la transcription et la réparation de l'ADN. Surexprimée dans les tissus en prolifération, y compris dans de nombreuses tumeurs, l'ASF1 est devenue une cible thérapeutique prometteuse. Ici, nous combinons des approches structurelles, informatiques et biochimiques pour concevoir des peptides qui inhibent l'interaction ASF1-histone. En partant de la structure du complexe ASF1-histone humain, nous avons mis au point une stratégie de conception rationnelle combinant la fixation des épitopes et l'optimisation des contacts d'interface pour identifier un puissant inhibiteur peptidique avec une constante de dissociation de 3 nM. Lorsqu'ils sont introduits dans des cellules en culture, les inhibiteurs entravent la prolifération cellulaire, perturbent la progression du cycle cellulaire et réduisent la migration et l'invasion des cellules d'une manière proportionnelle à leur affinité pour l'ASF1. Enfin, nous constatons que l'injection directe du plus puissant inhibiteur du peptide ASF1 dans les allogreffes de souris réduit la croissance des tumeurs. Nos résultats ouvrent de nouvelles voies pour utiliser les inhibiteurs de l'ASF1 comme des pistes prometteuses pour le traitement du cancer.

Published
2019

19. The H2A.J histone variant contributes to Interferon-Stimulated Gene expression in senescence by its weak interaction with H1 and the derepression of repeated DNA sequences

Author

Mangelinck, Adele, primary, Coudereau, Clement, additional, Courbeyrette, Regis, additional, Ouararhni, Khalid, additional, Hamiche, Ali, additional, Redon, Christophe E., additional, Bonner, William M., additional, Van Dijk, Erwin, additional, Derbois, Celine, additional, Olaso, Robert, additional, Deleuze, Jean-Francois, additional, Fenaille, Francois, additional, Ruebe, Claudia E., additional, Thuret, Jean-Yves, additional, and MANN, Carl, additional

Published
2020
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20. The importance of naturally attenuated SARS‐CoV‐2in the fight against COVID‐19

Author

Armengaud, Jean, primary, Delaunay‐Moisan, Agnès, additional, Thuret, Jean‐Yves, additional, van Anken, Eelco, additional, Acosta‐Alvear, Diego, additional, Aragón, Tomás, additional, Arias, Carolina, additional, Blondel, Marc, additional, Braakman, Ineke, additional, Collet, Jean‐François, additional, Courcol, René, additional, Danchin, Antoine, additional, Deleuze, Jean‐François, additional, Lavigne, Jean‐Philippe, additional, Lucas, Sophie, additional, Michiels, Thomas, additional, Moore, Edward R. B., additional, Nixon‐Abell, Jonathon, additional, Rossello‐Mora, Ramon, additional, Shi, Zheng‐Li, additional, Siccardi, Antonio G., additional, Sitia, Roberto, additional, Tillett, Daniel, additional, Timmis, Kenneth N., additional, Toledano, Michel B., additional, van der Sluijs, Peter, additional, and Vicenzi, Elisa, additional

Published
2020
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21. Civ1 (CAK in vivo), a novel Cdk-activating kinase

Author

Thuret, Jean-Yves, Valay, Jean-Gabriel, Faye, Gerard, and Mann, Carl

Subjects
Protein kinases -- Research, Phosphorylation -- Analysis, Saccharomyces -- Genetic aspects, Biological sciences
Abstract

Cyclin-dependent protein kinases (Cdks) are essential elements in the regulation of cell division and gene expression. To be active, Cdks usually require the binding of a cyclin and phosphorylation by a Cdk-activating kinase (CAK). Civ1 (CAK in vivo) was identified in Saccharomyces cerevisiae. The sequence of Civ1 has the greatest similarity to that of the Cdks. However, Civ1 is different in that it is active as a monomer. Thus, it could be the founding member of a novel family of kinases.

Published
1996

23. Ouabain and chloroquine trigger senolysis of BRAF‐V600E‐induced senescent cells by targeting autophagy.

Author

L'Hôte, Valentin, Courbeyrette, Régis, Pinna, Guillaume, Cintrat, Jean‐Christophe, Le Pavec, Gwenaëlle, Delaunay‐Moisan, Agnès, Mann, Carl, and Thuret, Jean‐Yves

Subjects
OUABAIN, CHLOROQUINE, AUTOPHAGY, ION transport (Biology), CELLULAR aging, CELL death
Abstract

The expression of BRAF‐V600E triggers oncogene‐induced senescence in normal cells and is implicated in the development of several cancers including melanoma. Here, we report that cardioglycosides such as ouabain are potent senolytics in BRAF senescence. Sensitization by ATP1A1 knockdown and protection by supplemental potassium showed that senolysis by ouabain was mediated by the Na,K‐ATPase pump. Both ion transport inhibition and signal transduction result from cardioglycosides binding to Na,K‐ATPase. An inhibitor of the pump that does not trigger signaling was not senolytic despite blocking ion transport, demonstrating that signal transduction is required for senolysis. Ouabain triggered the activation of Src, p38, Akt, and Erk in BRAF‐senescent cells, and signaling inhibitors prevented cell death. The expression of BRAF‐V600E increased ER stress and autophagy in BRAF‐senescent cells and sensitized the cell to senolysis by ouabain. Ouabain inhibited autophagy flux, which was restored by signaling inhibitors. Consequently, we identified autophagy inhibitor chloroquine as a novel senolytic in BRAF senescence based on the mode of action of cardioglycosides. Our work underlies the interest of characterizing the mechanisms of senolytics to discover novel compounds and identifies the endoplasmic reticulum stress‐autophagy tandem as a new vulnerability in BRAF senescence that can be exploited for the development of further senolytic strategies. [ABSTRACT FROM AUTHOR]

Published
2021
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24. Deacetylation of H4-K16Ac and heterochromatin assembly in senescence

Author

Contrepois Kévin, Thuret Jean-Yves, Courbeyrette Régis, Fenaille François, and Mann Carl

Subjects
Genetics, QH426-470
Abstract

Abstract Background Cellular senescence is a stress response of mammalian cells leading to a durable arrest of cell proliferation that has been implicated in tumor suppression, wound healing, and aging. The proliferative arrest is mediated by transcriptional repression of genes essential for cell division by the retinoblastoma protein family. This repression is accompanied by varying degrees of heterochromatin assembly, but little is known regarding the molecular mechanisms involved. Results We found that both deacetylation of H4-K16Ac and expression of HMGA1/2 can contribute to DNA compaction during senescence. SIRT2, an NAD-dependent class III histone deacetylase, contributes to H4-K16Ac deacetylation and DNA compaction in human fibroblast cell lines that assemble striking senescence-associated heterochromatin foci (SAHFs). Decreased H4-K16Ac was observed in both replicative and oncogene-induced senescence of these cells. In contrast, this mechanism was inoperative in a fibroblast cell line that did not assemble extensive heterochromatin during senescence. Treatment of senescent cells with trichostatin A, a class I/II histone deacetylase inhibitor, also induced rapid and reversible decondensation of SAHFs. Inhibition of DNA compaction did not significantly affect the stability of the senescent state. Conclusions Variable DNA compaction observed during senescence is explained in part by cell-type specific regulation of H4 deacetylation and HMGA1/2 expression. Deacetylation of H4-K16Ac during senescence may explain reported decreases in this mark during mammalian aging and in cancer cells.

Published
2012
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25. Glucocorticoids delay RAF-induced senescence promoted by EGR1

Author

Carvalho, Cyril, primary, L'Hôte, Valentin, additional, Courbeyrette, Régis, additional, Kratassiouk, Gueorgui, additional, Pinna, Guillaume, additional, Cintrat, Jean-Christophe, additional, Denby-Wilkes, Cyril, additional, Derbois, Céline, additional, Olaso, Robert, additional, Deleuze, Jean-François, additional, Mann, Carl, additional, and Thuret, Jean-Yves, additional

Published
2019
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27. RBE and Particle Therapy Biology Comparable Senescence Induction in Three-dimensional Human Cartilage Model by Exposure to Therapeutic Doses of X-rays or C-ions

Author

Hamdi , Dounia, Chevalier , François, Groetz , Jean-Emmanuel, Durantel , Florent, Thuret , Jean-Yves, Mann , Carl, Saintigny , Yannick, Laboratoire d'Accueil et de Recherche avec les Ions Accélérés (LARIA), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Génétique moléculaire et destin cellulaire (FRE 3377), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Accueil et de Recherche avec les Ions Accélérés ( LARIA ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique moléculaire et destin cellulaire ( FRE 3377 ), and Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
[ PHYS.PHYS.PHYS-MED-PH ] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Abstract

International audience; The relative biological effectiveness of carbon ions compared with X-rays scored 2.6 in primary human articular chondrocytes in 2-dimensional culture. This was correlated with stronger cellular senescence induction (two-fold). This differential effect was not reflected in the 3-dimensional cartilage model, as both ionizing radiation types induced comparable senescence. Carbon ions seem as safe as X-rays to articular cartilage in the context of radiation therapy.

Published
2016

28. Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression

Author

Contrepois, Kévin, primary, Coudereau, Clément, additional, Benayoun, Bérénice A., additional, Schuler, Nadine, additional, Roux, Pierre-François, additional, Bischof, Oliver, additional, Courbeyrette, Régis, additional, Carvalho, Cyril, additional, Thuret, Jean-Yves, additional, Ma, Zhihai, additional, Derbois, Céline, additional, Nevers, Marie-Claire, additional, Volland, Hervé, additional, Redon, Christophe E., additional, Bonner, William M., additional, Deleuze, Jean-François, additional, Wiel, Clotilde, additional, Bernard, David, additional, Snyder, Michael P., additional, Rübe, Claudia E., additional, Olaso, Robert, additional, Fenaille, François, additional, and Mann, Carl, additional

Published
2017
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29. A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus

Author

Lazorthes, Sandra, Vallot, Céline, Briois, Sébastien, Aguirrebengoa, Marion, Thuret, Jean-Yves, St Laurent, Georges, Rougeulle, Claire, Kapranov, Philipp, Mann, Carl, Trouche, Didier, Nicolas, Estelle, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et de Technologies de Saclay (IBITECS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Sénescence et stabilité génomique (SEN), Département Biologie des Génomes (DBG), Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), St Laurent Institute, St. Laurent Institute, Institute of Genomics, Huaqiao University School of Medicine, Xiamen, Academy of Biology and Biotechnology, Southern Federal University [Rostov-on-Don] (SFEDU), LBCMCP, Centre National de la Recherche Scientifique ( CNRS ), Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie et de Technologies de Saclay ( IBITECS ), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Sénescence et stabilité génomique ( SEN ), Département Biologie des Génomes ( DBG ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Woburn, Massachusetts, Southern Federal University - Rostov on Don, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH : Cell Line, RNA, Untranslated, MESH : RNA, Untranslated, MESH: Humans, MESH : Chromatin, [ SDV ] Life Sciences [q-bio], MESH : Cell Aging, MESH : Heterochromatin, [SDV]Life Sciences [q-bio], MESH : Humans, Chromatin, Article, Cell Line, MESH: Cell Line, MESH: Chromatin, MESH: RNA, Untranslated, MESH: Heterochromatin, MESH: Cell Aging, Heterochromatin, Humans, Erratum, ComputingMilieux_MISCELLANEOUS, Cellular Senescence
Abstract

Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anticancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. Here we analyze strand-specific transcriptome changes during oncogene-induced human senescence. Strikingly, while differentially expressed RNAs are mostly repressed during senescence, ncRNAs belonging to the recently described vlincRNA (very long intergenic ncRNA) class are mainly activated. We show that VAD, a novel antisense vlincRNA strongly induced during senescence, is required for the maintenance of senescence features. VAD modulates chromatin structure in cis and activates gene expression in trans at the INK4 locus, which encodes cell cycle inhibitors important for senescence-associated cell proliferation arrest. Importantly, VAD inhibits the incorporation of the repressive histone variant H2A.Z at INK4 gene promoters in senescent cells. Our data underline the importance of vlincRNAs as sensors of cellular environment changes and as mediators of the correct transcriptional response., Senescence is associated with chromatin reorganization in heterochromatin foci. Here the authors show that VAD, a very long intergenic non-coding RNA activated by senescence, inhibits the incorporation of the repressive histone variant H2A.Z to INK4 promoters in senescent cells.

Published
2015

30. Erratum: A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus

Author

Lazorthes, Sandra, primary, Vallot, Céline, additional, Briois, Sébastien, additional, Aguirrebengoa, Marion, additional, Thuret, Jean-Yves, additional, Laurent, Georges St., additional, Rougeulle, Claire, additional, Kapranov, Philipp, additional, Mann, Carl, additional, Trouche, Didier, additional, and Nicolas, Estelle, additional

Published
2015
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31. Global Reorganization of the Nuclear Landscape in Senescent Cells

Author

Chandra, Tamir, primary, Ewels, Philip Andrew, additional, Schoenfelder, Stefan, additional, Furlan-Magaril, Mayra, additional, Wingett, Steven William, additional, Kirschner, Kristina, additional, Thuret, Jean-Yves, additional, Andrews, Simon, additional, Fraser, Peter, additional, and Reik, Wolf, additional

Published
2015
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33. Protein folding activity of ribosomal rna is a selective target of two unrelated antiprion drugs

Author

Tribouillard-Tanvier, Déborah, Reis, Suzana Dos, Gug, Fabienne, Voisset, Cécile, Béringue, Vincent, Sabate, Raimon, Kikovska, Ema, Talarek, Nicolas, Bach, Stéphane, Huang, Chenhui, Desban, Nathalie, Saupe, Sven J., Supattapone, Surachai, Thuret, Jean-Yves, Chédin, Stéphane, Vilette, Didier, Galons, Hervé, Sanyal, Suparna, Blondel, Marc, Tribouillard-Tanvier, Déborah, Reis, Suzana Dos, Gug, Fabienne, Voisset, Cécile, Béringue, Vincent, Sabate, Raimon, Kikovska, Ema, Talarek, Nicolas, Bach, Stéphane, Huang, Chenhui, Desban, Nathalie, Saupe, Sven J., Supattapone, Surachai, Thuret, Jean-Yves, Chédin, Stéphane, Vilette, Didier, Galons, Hervé, Sanyal, Suparna, and Blondel, Marc

Abstract

Background: 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases.Methodology/Principal Findings: Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome.Conclusion/Significance: 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity.

Published
2010

34. Protein Folding Activity of Ribosomal RNA Is a Selective Target of Two Unrelated Antiprion Drugs

Author

Tribouillard-Tanvier, Deborah, Dos Reis, Suzana, Gug, Fabienne, Voisset, Cecile, Beringue, Vincent, Sabate, Raimon, Kikovska, Ema, Talarek, Nicolas, Bach, Stephane, Huang, Chenhui, Desban, Nathalie, Saupe, Sven J., Supattapone, Surachai, Thuret, Jean-Yves, Chedin, Stephane, Vilette, Didier, Galons, Herve, Sanyal, Suparna, Blondel, Marc, Tribouillard-Tanvier, Deborah, Dos Reis, Suzana, Gug, Fabienne, Voisset, Cecile, Beringue, Vincent, Sabate, Raimon, Kikovska, Ema, Talarek, Nicolas, Bach, Stephane, Huang, Chenhui, Desban, Nathalie, Saupe, Sven J., Supattapone, Surachai, Thuret, Jean-Yves, Chedin, Stephane, Vilette, Didier, Galons, Herve, Sanyal, Suparna, and Blondel, Marc

Abstract

Background: 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases. Methodology/Principal Findings: Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome. Conclusion/Significance: 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity.

Published
2008
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35. Independence of Repressive Histone Marks and Chromatin Compaction during Senescent Heterochromatic Layer Formation

Author

Chandra, Tamir, primary, Kirschner, Kristina, additional, Thuret, Jean-Yves, additional, Pope, Benjamin D., additional, Ryba, Tyrone, additional, Newman, Scott, additional, Ahmed, Kashif, additional, Samarajiwa, Shamith A., additional, Salama, Rafik, additional, Carroll, Thomas, additional, Stark, Rory, additional, Janky, Rekin's, additional, Narita, Masako, additional, Xue, Lixiang, additional, Chicas, Agustin, additional, Nũnez, Sabrina, additional, Janknecht, Ralf, additional, Hayashi-Takanaka, Yoko, additional, Wilson, Michael D., additional, Marshall, Aileen, additional, Odom, Duncan T., additional, Babu, M. Madan, additional, Bazett-Jones, David P., additional, Tavaré, Simon, additional, Edwards, Paul A.W., additional, Lowe, Scott W., additional, Kimura, Hiroshi, additional, Gilbert, David M., additional, and Narita, Masashi, additional

Published
2012
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39. Protein Folding Activity of Ribosomal RNA Is a Selective Target of Two Unrelated Antiprion Drugs

Author

Tribouillard-Tanvier, Déborah, primary, Dos Reis, Suzana, additional, Gug, Fabienne, additional, Voisset, Cécile, additional, Béringue, Vincent, additional, Sabate, Raimon, additional, Kikovska, Ema, additional, Talarek, Nicolas, additional, Bach, Stéphane, additional, Huang, Chenhui, additional, Desban, Nathalie, additional, Saupe, Sven J., additional, Supattapone, Surachai, additional, Thuret, Jean-Yves, additional, Chédin, Stéphane, additional, Vilette, Didier, additional, Galons, Hervé, additional, Sanyal, Suparna, additional, and Blondel, Marc, additional

Published
2008
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43. Human CDK10 Gene Isoforms

Author

Sergère, Jean-Christophe, primary, Thuret, Jean-Yves, additional, Roux, Gwenaëlle Le, additional, Carosella, Edgardo D., additional, and Leteurtre, François, additional

Published
2000
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44. Specificity of Cdk activation in vivo by the two Caks Mcs6 and Csk1 in fission yeast.

Author

Hermand, Damien, Westerling, Thomas, Pihlak, Arno, Thuret, Jean-Yves, Vallenius, Tea, Tiainen, Marianne, Vandenhaute, Jean, Cottarel, Guillaume, Mann, Carl, and Mäkelä, Tomi P.

Subjects
PHOSPHORYLATION, PROTEIN kinases, GENOTYPE-environment interaction, PHENOTYPES, YEAST, PLANT propagation
Abstract

Activating phosphorylation of cyclin-dependent kinases (Cdks) is mediated by at least two structurally distinct types of Cdk-activating kinases (Caks): the trimeric Cdk7-cyclin H-Mat1 complex in metazoans and the single-subunit Cak1 in budding yeast. Fission yeast has both Cak types: Mcs6 is a Cdk7 ortholog and Csk1 a single-subunit kinase. Both phosphorylate Cdks in vitro and rescue a thermosensitive budding yeast CAK1 strain. However, this apparent redundancy is not observed in fission yeast in vivo. We have identified mutants that exhibit phenotypes attributable to defects in either Mcs6-activating phosphorylation or in Cdc2-activating phosphorylation. Mcs6, human Cdk7 and budding yeast Cak1 were all active as Caks for Cdc2 when expressed in fission yeast. Although Csk1 could activate Mcs6, it was unable to activate Cdc2. Biochemical experiments supported these genetic results: budding yeast Cak1 could bind and phosphorylate Cdc2 from fission yeast lysates, whereas fission yeast Csk1 could not. These results indicate that Mcs6 is the direct activator of Cdc2, and Csk1 only activates Mcs6. This demonstrates in vivo specificity in Cdk activation by Caks. [ABSTRACT FROM AUTHOR]

Published
2001
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45. Human CDK10 Gene Isoforms

Author

Serge`re, Jean-Christophe, Thuret, Jean-Yves, Le, Gwenae¨lle, Edgardo, Roux, Carosella, D., and Leteurtre, Franc¸ois

Abstract

The CDK10/PISSLRE gene has been shown to encode two different CDK-like putative kinases. The function(s) of the gene products are unknown, although a role at the G2/M transition has been suggested. We characterised two novel cDNAs. CDK10 mRNA quantity was not found to be correlated with cell proliferation status in HeLa or WI38 cell cultures or in human tissues. Relative levels of the four CDK10 isoforms were studied by RT-PCR, of which three were principally expressed. The two initially cloned isoforms predominated in human tissues, except in brain and muscle. Relative isoform levels did not vary during the cell cycle in culture, except when cells entered into the cell cycle. Finally, the predominant isoforms were shown to have different translation initiation sites and to have different subcellular distribution, due to an alternatively spliced nuclear localisation signal.

Published
2000
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46. Protein folding activity of ribosomal rna is a selective target of two unrelated antiprion drugs

Author

Tribouillard-Tanvier, Déborah, Reis, Suzana Dos, Gug, Fabienne, Voisset, Cécile, Béringue, Vincent, Sabate, Raimon, Kikovska, Ema, Talarek, Nicolas, Bach, Stéphane, Huang, Chenhui, Desban, Nathalie, Saupe, Sven J., Supattapone, Surachai, Thuret, Jean-Yves, Chédin, Stéphane, Vilette, Didier, Galons, Hervé, Sanyal, Suparna, Blondel, Marc, Tribouillard-Tanvier, Déborah, Reis, Suzana Dos, Gug, Fabienne, Voisset, Cécile, Béringue, Vincent, Sabate, Raimon, Kikovska, Ema, Talarek, Nicolas, Bach, Stéphane, Huang, Chenhui, Desban, Nathalie, Saupe, Sven J., Supattapone, Surachai, Thuret, Jean-Yves, Chédin, Stéphane, Vilette, Didier, Galons, Hervé, Sanyal, Suparna, and Blondel, Marc

Abstract

Background: 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases.Methodology/Principal Findings: Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome.Conclusion/Significance: 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity.

49. Ready for an orange revolution in biotechnology?

Author

Thuret JY and Blondel M

Subjects
Biological Assay methods, Biotechnology methods, Genomics methods, Protein Interaction Mapping methods, Saccharomyces cerevisiae drug effects, Biological Assay trends, Biotechnology trends, Drug Design, Genomics trends, Protein Interaction Mapping trends, Saccharomyces cerevisiae physiology, Saccharomyces cerevisiae Proteins physiology
Published
2006
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