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141 results on '"Cabantous, Stéphanie"'

1. Human septins organize as octamer-based filaments and mediate actin-membrane anchoring in cells

Author

Martins, Carla Silva, Taveneau, Cyntia, Castro-Linares, Gerard, Baibakov, Mikhail, Buzhinsky, Nicolas, Eroles, Mar, Milanović, Violeta, Omi, Shizue, Pedelacq, Jean-Denis, Iv, Francois, Bouillard, Léa, Llewellyn, Alexander, Gomes, Maxime, Belhabib, Mayssa, Kuzmić, Mira, Verdier-Pinard, Pascal, Lee, Stacey, Badache, Ali, Kumar, Sanjay, Chandre, Cristel, Brasselet, Sophie, Rico, Felix, Rossier, Olivier, Koenderink, Gijsje H, Wenger, Jerome, Cabantous, Stéphanie, and Mavrakis, Manos

Subjects
Biochemistry and Cell Biology, Biological Sciences, Bioengineering, Nanotechnology, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Humans, Actins, Cell Membrane, Cytoskeleton, Microscopy, Septins, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Septins are cytoskeletal proteins conserved from algae and protists to mammals. A unique feature of septins is their presence as heteromeric complexes that polymerize into filaments in solution and on lipid membranes. Although animal septins associate extensively with actin-based structures in cells, whether septins organize as filaments in cells and if septin organization impacts septin function is not known. Customizing a tripartite split-GFP complementation assay, we show that all septins decorating actin stress fibers are octamer-containing filaments. Depleting octamers or preventing septins from polymerizing leads to a loss of stress fibers and reduced cell stiffness. Super-resolution microscopy revealed septin fibers with widths compatible with their organization as paired septin filaments. Nanometer-resolved distance measurements and single-protein tracking further showed that septin filaments are membrane bound and largely immobilized. Finally, reconstitution assays showed that septin filaments mediate actin-membrane anchoring. We propose that septin organization as octamer-based filaments is essential for septin function in anchoring and stabilizing actin filaments at the plasma membrane.

Published
2023

9. Human septins organize as octamer-based filaments and mediate actin-membrane anchoring in cells

Author

Martins, Carla Silva, primary, Taveneau, Cyntia, additional, Castro-Linares, Gerard, additional, Baibakov, Mikhail, additional, Buzhinsky, Nicolas, additional, Eroles, Mar, additional, Milanović, Violeta, additional, Omi, Shizue, additional, Pedelacq, Jean-Denis, additional, Iv, Francois, additional, Bouillard, Léa, additional, Llewellyn, Alexander, additional, Gomes, Maxime, additional, Belhabib, Mayssa, additional, Kuzmić, Mira, additional, Verdier-Pinard, Pascal, additional, Lee, Stacey, additional, Badache, Ali, additional, Kumar, Sanjay, additional, Chandre, Cristel, additional, Brasselet, Sophie, additional, Rico, Felix, additional, Rossier, Olivier, additional, Koenderink, Gijsje H., additional, Wenger, Jerome, additional, Cabantous, Stéphanie, additional, and Mavrakis, Manos, additional

Published
2022
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10. Tripartite split-GFP assay to identify selective intracellular nanobody that suppresses GTPase RHOA subfamily downstream signaling

Author

Keller, Laura, primary, Tardy, Claudine, additional, Ligat, Laetitia, additional, Le Pennec, Soazig, additional, Bery, Nicolas, additional, Koraïchi, Faten, additional, Chinestra, Patrick, additional, David, Mélissa, additional, Gence, Rémi, additional, Favre, Gilles, additional, Cabantous, Stéphanie, additional, and Olichon, Aurélien, additional

Published
2022
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12. Ubiquitinating enzymes as potential therapeutic targets to prevent muscle atrophy – The case of MuRF1/ TRIM63

Author

Malige, Mélodie, Peris-Moreno, Dulce, Cabantous, Stéphanie, Claustre, Agnes, Armani, Andrea, Sandri, Marco, Taillandier, Daniel, Polge, Cécile, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Venetian Institute Molecular Medicine (VIMM), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), AFM-téléthon Grants #16438 and #21026, #23792, Fondation pour la Recherche Médicale (FRM) Grant number DEQ20180339180, and COST Action ProteoCure

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

13. Human septins in cells organize as octamer-based filaments mediating actin-membrane anchoring

Author

Martins, Carla Silva, primary, Taveneau, Cyntia, additional, Castro-Linares, Gerard, additional, Baibakov, Mikhail, additional, Buzhinsky, Nicolas, additional, Eroles, Mar, additional, Milanović, Violeta, additional, Iv, Francois, additional, Bouillard, Léa, additional, Llewellyn, Alex, additional, Gomes, Maxime, additional, Belhabib, Mayssa, additional, Kuzmić, Mira, additional, Verdier-Pinard, Pascal, additional, Lee, Stacey, additional, Badache, Ali, additional, Kumar, Sanjay, additional, Chandre, Cristel, additional, Brasselet, Sophie, additional, Rico, Felix, additional, Rossier, Olivier, additional, Koenderink, Gijsje H., additional, Wenger, Jerome, additional, Cabantous, Stéphanie, additional, and Mavrakis, Manos, additional

Published
2022
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14. Additional file 1 of Solution structure of the type I polyketide synthase Pks13 from Mycobacterium tuberculosis

Author

Bon, Cécile, Cabantous, Stéphanie, Julien, Sylviane, Guillet, Valérie, Chalut, Christian, Rima, Julie, Brison, Yoann, Malaga, Wladimir, Sanchez-Dafun, Angelique, Gavalda, Sabine, Quémard, Annaïk, Marcoux, Julien, Waldo, Geoffrey S., Guilhot, Christophe, and Mourey, Lionel

Abstract

Additional file 1: Figure S1. Mycolic acid condensation by Pks13. Figure S2. Native mass spectrometry analysis of Pks13. Figure S3. Bottom-up proteomic analysis of Pks13(S1533A) incubated without C16-CoA. Figure S4. Bottom-up proteomic analysis of Pks13(S1533A) incubated with C16-CoA. Figure S5. Gel filtration chromatograms of full-length enzymes. Figure S6. Comparison of the Pks13, fACP1-KS-AT and fACP2-TE envelopes. Figure S7. Impact of ionic strength on Pks13 activity. Figure S8. Analysis of concentration dependence for SAXS data collected in batch mode. Figure S9. Guinier analysis and plot of ln I(S) versus ln(S) for the various constructs. Table S1. DLS analysis of the various Pks13 entities studied. Table S2. Essential details about samples, SAXS data acquisition and analysis, modelling fitting and software used.

Published
2022
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15. Insights into animal septins using recombinant human septin octamers with distinct SEPT9 isoforms

Author

Iv, Francois, primary, Martins, Carla Silva, additional, Castro-Linares, Gerard, additional, Taveneau, Cyntia, additional, Barbier, Pascale, additional, Verdier-Pinard, Pascal, additional, Camoin, Luc, additional, Audebert, Stéphane, additional, Tsai, Feng-Ching, additional, Ramond, Laurie, additional, Llewellyn, Alex, additional, Belhabib, Mayssa, additional, Nakazawa, Koyomi, additional, Di Cicco, Aurélie, additional, Vincentelli, Renaud, additional, Wenger, Jerome, additional, Cabantous, Stéphanie, additional, Koenderink, Gijsje H., additional, Bertin, Aurélie, additional, and Mavrakis, Manos, additional

Published
2021
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16. Vγ9Vδ2 T Cells Activation Through Phosphoantigens Can Be Impaired by a RHOB Rerouting in Lung Cancer

Author

Laplagne, Chloé, Meddour, Sarah, Figarol, Sarah, Michelas, Marie, Calvayrac, Olivier, Favre, Gilles, Laurent, Camille, Fournié, Jean-Jacques, Cabantous, Stéphanie, Poupot, Mary, Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Calvayrac, Olivier

Subjects
[SDV] Life Sciences [q-bio], phosphoantigen, endosomes, [SDV]Life Sciences [q-bio], TCR activation, [SDV.IMM]Life Sciences [q-bio]/Immunology, RHOB, Vγ9Vδ2 T cells, ComputingMilieux_MISCELLANEOUS, split-GFP
Abstract

International audience; Vγ9Vδ2 T cells are known to be efficient anti-tumor effectors activated through phosphoantigens (PAg) that are naturally expressed by tumor cells or induced by amino bisphosphonates treatment. This PAg-activation which is TCR and butyrophilin BTN3A dependent can be modulated by NKG2D ligands, immune checkpoint ligands, adhesion molecules, and costimulatory molecules. This could explain the immune-resistance observed in certain clinical trials based on Vγ9Vδ2 T cells therapies. In NSCLC, encouraging responses were obtained with zoledronate administrations for 50% of patients. According to the in vivo results, we showed that the in vitro Vγ9Vδ2 T cell reactivity depends on the NSCLC cell line considered. If the PAg-pretreated KRAS mutated A549 is highly recognized and killed by Vγ9Vδ2 T cells, the EGFR mutated PC9 remains resistant to these killers despite a pre-treatment either with zoledronate or with exogenous BrHPP. The immune resistance of PC9 was shown not to be due to immune checkpoint ligands able to counterbalance NKG2D ligands or adhesion molecules such as ICAM-1 highly expressed by PC9. RHOB has been shown to be involved in the Vγ9Vδ2 TCR signaling against these NSCLC cell lines, in this study we therefore focused on its intracellular behavior. In comparison to a uniform distribution of RHOB in endosomes and at the plasma membrane in A549, the presence of large endosomal clusters of RHOB was visualized by a split-GFP system, suggesting that RHOB rerouting in the PC9 tumor cell could impair the reactivity of the immune response.

Published
2020

18. In the UPS family, which E2 enzymes collaborate with the E3 ligase MuRF1, a major actor ofmuscle atrophy?

Author

Polge, Cécile, Cabantous, Stéphanie, Claustre, Agnes, Deval, Christiane, Combaret, Lydie, Attaix, Didier, Taillandier, Daniel, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), and 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)

Subjects
ubiquitin conjugating enzyme UBE2, E3 ubiquitin ligase, muscle wasting, MuRF1, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Muscle wasting is associated with many diseases and also physiological conditions (disuse, aging). Skeletalmuscle mass is largely controlled by the ubiquitin-proteasome system (UPS) and thus by the ubiquitinatingenzymes (E2s and E3s) that target substrates for subsequent degradation. MuRF1 is the only E3 known to targetcontractile proteins (α-actin, myosins) during catabolic situations. MuRF1 knock-out partially protected skeletalmuscles from atrophy in denervated or immobilized animals. MuRF1 is therefore a putative target for preventingmuscle wasting. However, MuRF1 depends on E2 ubiquitin conjugating enzymes for ubiquitin chain formation onthe substrates.In this work, we demonstrated that only highly sensitive and complementary interactomic approaches (SurfacePlasmon Resonance, Yeast three-Hybrid and split-GFP) allowed the identification of MuRF1 E2 partners. Amongthe 14 E2 expressed in muscle, 5 physically and functionally interacted with MuRF1. We also showed thattelethonin, a MuRF1 substrate, governed the affinity between MuRF1 and two of these E2s. We are currentlystudying the capacity of E2-MuRF1 duos to target the main contractile proteins both in vitro and in vivo.We report here the first MuRF1-E2s network, which may prove valuable for deciphering the precise mechanismsinvolved in the atrophying muscle program and for proposing new therapeutic approaches.

Published
2019

22. Cytoplasmic p27 Kip1 promotes tumorigenesis via suppression of RhoB activity

Author

Calvayrac, Olivier, Nowosad, Ada, Cabantous, Stéphanie, Lin, Lin-Po, Figarol, Sarah, Jeannot, Pauline, Serres, Murielle, Callot, Caroline, Perchey, Renaud, Creff, Justine, Taranchon-Clermont, Estelle, Rouquette, Isabelle, Favre, Gilles, Pradines, Anne, Manenti, Stéphane, Mazières, Julien, Lee, Huei, Besson, Arnaud, Lin, Lin‐Po, Taranchon‐Clermont, Estelle, Centre de Recherches en Cancérologie de Toulouse (CRCT), 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 National de Ressources Génomiques Végétales (CNRGV), Institut National de la Recherche Agronomique (INRA), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Registre Multicentrique à Vocation Nationale des Mésothéliomes Pleuraux (MESONAT), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Service de Pneumologie, CHU, Hôpital Larrey, 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (CPTP), 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)-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)-Institut Claudius Regaud, Hôpital Larrey [Toulouse], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]

Subjects
0301 basic medicine, RHOB, [SDV]Life Sciences [q-bio], Cell, transgenic mice, medicine.disease_cause, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, non-small cell lung carcinoma, Cyclin-dependent kinase, medicine, Protein kinase B, PI3K/AKT/mTOR pathway, p27/Kip1, biology, Oncogene, RhoB, Cell cycle, 3. Good health, lung cancer, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Carcinogenesis
Abstract

International audience; The cell cycle inhibitor p27Kip1 is a tumor suppressor via the inhibition of CDK complexes in the nucleus. However, p27 also plays other functions in the cell and may acquire oncogenic roles when located in the cytoplasm. Activation of oncogenic pathways such as Ras or PI3K/AKT causes the relocalization of p27 in the cytoplasm, where it can promote tumorigenesis by unclear mechanisms. Here, we investigated how cytoplasmic p27 participates in the development of non-small cell lung carcinomas. We provide molecular and genetic evidence that the oncogenic role of p27 is mediated, at least in part, by binding to and inhibiting the GTPase RhoB, which normally acts as a tumor suppressor in the lung. Genetically modified mice revealed that RhoB expression is preferentially lost in tumors in which p27 is absent and maintained in tumors expressing wild-type p27 or p27CK- , a mutant that cannot inhibit CDKs. Moreover, although the absence of RhoB promoted tumorigenesis in p27-/- animals, it had no effect in p27CK- knock-in mice, suggesting that cytoplasmic p27 may act as an oncogene, at least in part, by inhibiting the activity of RhoB. Finally, in a cohort of lung cancer patients, we identified a subset of tumors harboring cytoplasmic p27 in which RhoB expression is maintained and these characteristics were strongly associated with decreased patient survival. Thus, monitoring p27 localization and RhoB levels in non-small cell lung carcinoma patients appears to be a powerful prognostic marker for these tumors. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2018

26. Identification of a muscle-specific MuRF1-E2 network

Author

Cabantous, Stéphanie, Deval, Christiane, Claustre, Agnes, Bouchenot, Catherine, Combaret, Lydie, Taillandier, Daniel, and Polge, Cécile

Subjects
atrophie du muscle squelettique, physiology, Alimentation et Nutrition, Chimie analytique, protéine myofibrillaire, Food and Nutrition, approche interactomique, Analytical chemistry, Physiologie
Abstract

As a result of an imbalance between protein synthesis and proteolysis, important protein losses occur during various physiological and pathological situations. Skeletal muscle mass is largely controlled by the ubiquitin proteasome system and thus by ubiquitinating enzymes. This proteolytic system is highly regulated and controls precisely the activity of numerous cellular proteins that are first tagged by a polyubiquitin chain on an internal lysine. Ubiquitination is based on the sequential action of the E1-activating enzyme, an E2 ubiquitin-conjugating enzyme (38 members) and an E3 ligase (> 600 members). The E1 enzyme activates the ubiquitin that it is transferred to an E2. E3 ligases recruit and bind specific substrates. MuRF1, a muscle-speci_c E3, is the only E3 ligase known to target contractile proteins (α-actin,myosins) for degradation during catabolic situations. MuRF1 is therefore a putative target for preventing muscle wasting. However, RING E3s like MuRF1 highly depend on ubiquitin conjugating enzymes E2s for ubiquitin chain formation. Our main objective was then to identify the E2s working in concert with MuRF1 to target myofibrillar proteins in atrophying skeletal muscles. We focused on 12 E2 enzymes that are expressed in the skeletal muscle or in atrophying skeletal muscles. Classical biochemical approach such as pull-down did not allow identifying any MuRF1 interacting partner among these E2s, suggesting that E2-MuRF1 interactions are weak and/or transient, consistent with previous studies reporting that E2-E3 interactions range from moderate to weak. We demonstrated that only sensitive and complementary interactomic approaches (Surface Plasmon Resonance, Yeast three-Hybrid and split-GFP) allowed the identi_cation of MuRF1 E2 partners. We identified five E2 enzymes that physically interacted with MuRF1. We showed that these E2s functionally interacted with MuRF1 since, in contrast with the non-interacting E2D2, their co-expression in HEK293T cells with MuRF1 led to increased MuRF1 substrate degradation. In conclusion,we report the first MuRF1-E2s network. This may prove valuable for deciphering the precise mechanisms involved in the muscle-atrophying program and for proposing new therapeutically

Published
2017

28. A muscle-specific MuRF1-E2 network requires stabilization of MuRF1-E2 complexes by telethonin, a newly identified substrate

Author

Polge, Cécile, primary, Cabantous, Stéphanie, additional, Deval, Christiane, additional, Claustre, Agnès, additional, Hauvette, Antoine, additional, Bouchenot, Catherine, additional, Aniort, Julien, additional, Béchet, Daniel, additional, Combaret, Lydie, additional, Attaix, Didier, additional, and Taillandier, Daniel, additional

Published
2017
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31. Vitalité politique en rase campagne

Author

Bourdeau, Vincent, Cottin-Marx, Simon, Flipo, Fabrice, Grisoni, Anahita, Jouffe, Yves, Lagneau, Antoine, Le Blanc, Antoine, Michel, Olivier, Binctin, Barnabé, Cabantous, Stéphanie, Poulteau, Ève, Logiques de l'Agir ( UR 2274) (LdA), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Techniques, Territoires et Sociétés (LATTS), Université Paris-Est Marne-la-Vallée (UPEM)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Changement Social et Politique (LCSP (EA_7335)), Université Paris Diderot - Paris 7 (UPD7), Environnement Ville Société (EVS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Lyon (ENSAL)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale des Travaux Publics de l'État (ENTPE)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Laboratoire Ville, Mobilité, Transport (LVMT ), École des Ponts ParisTech (ENPC)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Paris-Est Marne-la-Vallée (UPEM), Institut d'Aménagement et d'Urbanisme de la Région d'Ile-de-France (IAU Île-de-France), Territoires, Villes, Environnement & Société - ULR 4477 (TVES), Université du Littoral Côte d'Opale (ULCO)-Université de Lille, Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Logiques de l'Agir ( EA 2274) (LdA), École normale supérieure - Lyon (ENS Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Paris-Est Marne-la-Vallée (UPEM)-École des Ponts ParisTech (ENPC), Université de Lille-Université du Littoral Côte d'Opale (ULCO), Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), and 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)

Subjects
ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract

International audience

Published
2015

33. Cytoplasmic p27Kip1 promotes tumorigenesis via suppression of RhoB activity.

Author

Calvayrac, Olivier, Nowosad, Ada, Cabantous, Stéphanie, Lin, Lin‐Po, Figarol, Sarah, Jeannot, Pauline, Serres, Murielle P, Callot, Caroline, Perchey, Renaud T, Creff, Justine, Taranchon‐Clermont, Estelle, Rouquette, Isabelle, Favre, Gilles, Pradines, Anne, Manenti, Stephane, Mazieres, Julien, Lee, Huei, and Besson, Arnaud

Abstract

The cell cycle inhibitor p27Kip1 is a tumor suppressor via the inhibition of CDK complexes in the nucleus. However, p27 also plays other functions in the cell and may acquire oncogenic roles when located in the cytoplasm. Activation of oncogenic pathways such as Ras or PI3K/AKT causes the relocalization of p27 in the cytoplasm, where it can promote tumorigenesis by unclear mechanisms. Here, we investigated how cytoplasmic p27 participates in the development of non‐small cell lung carcinomas. We provide molecular and genetic evidence that the oncogenic role of p27 is mediated, at least in part, by binding to and inhibiting the GTPase RhoB, which normally acts as a tumor suppressor in the lung. Genetically modified mice revealed that RhoB expression is preferentially lost in tumors in which p27 is absent and maintained in tumors expressing wild‐type p27 or p27CK–, a mutant that cannot inhibit CDKs. Moreover, although the absence of RhoB promoted tumorigenesis in p27−/− animals, it had no effect in p27CK– knock‐in mice, suggesting that cytoplasmic p27 may act as an oncogene, at least in part, by inhibiting the activity of RhoB. Finally, in a cohort of lung cancer patients, we identified a subset of tumors harboring cytoplasmic p27 in which RhoB expression is maintained and these characteristics were strongly associated with decreased patient survival. Thus, monitoring p27 localization and RhoB levels in non‐small cell lung carcinoma patients appears to be a powerful prognostic marker for these tumors. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2019
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34. Éditorial

Author

Bourdeau, Vincent, primary, Cottin-Marx, Simon, additional, Flipo, Fabrice, additional, Grisoni, Anahita, additional, Jouffe, Yves, additional, Lagneau, Antoine, additional, Leblanc, Antoine, additional, Michel, Olivier, additional, Binctin, Barnabé, additional, Cabantous, Stéphanie, additional, and Poulteau, Ève, additional

Published
2015
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35. Hybrid QM/MM vs Pure MM Molecular Dynamics for Evaluating Water Distribution within p21N-rasand the Resulting GTP Electronic Density

Author

Tichauer, Ruth H., Favre, Gilles, Cabantous, Stéphanie, and Brut, Marie

Abstract

p21rasprotein activity, regulated by GTP hydrolysis, constitutes an active field of research for the development of cancer targeted therapies that would concern ∼30% of human tumors to which specific mutations have been associated. Indeed, the catalyzing mechanisms provided by the protein environment during GTP hydrolysis and how they are impaired by specific mutations remain to be fully elucidated. In this article, we present results from molecular mechanics (MM) molecular dynamics (MD) simulations and density functional theory (DFT) calculations carried out for wild-type p21N-rasand six Gln 61 mutants. In the first part, we present the water distribution within the active site of the wild-type protein according to MM MD. Significant differences are observed when comparing the results to the previous distribution assessed through quantum mechanics/molecular mechanics (QM/MM) MD. Such method-dependent results highlight the importance of accounting for the electrostatic coupling between the protein complex and the solvent molecules in identifying hydration sites. In the second part, we present the results from DFT calculations performed to determine the electronic distribution of the GTP ligand, considering the wild-type active site arrangement according to both classical and hybrid approaches. Only in the QM/MM-based configuration is the ligand electronic density similar to that of a GDP-like state observed experimentally. For this reason, in the last set of calculations carried out for p21N-rasGln 61 mutants, only the active site structural conformations obtained through hybrid MD are considered. Through the analysis of the GTP electronic density, we conclude that the wild-type active site arrangement according to QM/MM MD is closer to a catalytically efficient conformation of the protein than the arrangement according to MM MD. Hence, water distribution according to the hybrid approach must correspond to the optimal placement of solvent in the active site. Within all of the studied Gln 61 substituted proteins, p21rasmajor catalyzing effect, which consists of stabilizing a more GDP-like state, is lost.

Published
2019
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