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1. Lactobacillus stress protein GroEL prevents colonic inflammation

Author

Dias, Alexandre M. M., Douhard, Romain, Hermetet, François, Regimbeau, Mathilde, Lopez, Tatiana E., Gonzalez, Daniel, Masson, Sophie, Marcion, Guillaume, Chaumonnot, Killian, Uyanik, Burhan, Causse, Sébastien Z., Rieu, Aurélie, Hadi, Tarik, Basset, Christelle, Chluba, Johanna, Grober, Jacques, Guzzo, Jean, Neiers, Fabrice, Ortega-Deballon, Pablo, Demidov, Oleg N., Lirussi, Frédéric, and Garrido, Carmen

Published
2021
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2. Selecting the first chemical molecule inhibitor of HSP110 for colorectal cancer therapy

Author

Gozzi, Gustavo J., Gonzalez, Daniel, Boudesco, Christophe, Dias, Alexandre M. M., Gotthard, Guillaume, Uyanik, Burhan, Dondaine, Lucile, Marcion, Guillaume, Hermetet, François, Denis, Camille, Hardy, Laurianne, Suzanne, Peggy, Douhard, Romain, Jego, Gaetan, Dubrez, Laurence, Demidov, Oleg N., Neiers, Fabrice, Briand, Loïc, Sopková-de Oliveira Santos, Jana, Voisin-Chiret, Anne-Sophie, and Garrido, Carmen

Published
2020
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3. HSP110 translocates to the nucleus upon genotoxic chemotherapy and promotes DNA repair in colorectal cancer cells

Author

Causse, Sebastien Z., Marcion, Guillaume, Chanteloup, Gaëtan, Uyanik, Burhan, Boudesco, Christophe, Grigorash, Bogdan B., Douhard, Romain, Dias, Alexandre M. M., Dumetier, Baptiste, Dondaine, Lucile, Gozzi, Gustavo J., Moussay, Etienne, Paggetti, Jérôme, Mirjolet, Céline, de Thonel, Aurélie, Dubrez, Laurence, Demidov, Oleg N., Gobbo, Jessica, and Garrido, Carmen

Published
2019
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5. Correction: DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues

Author

Glorian, Valérie, Allègre, Jennifer, Berthelet, Jean, Dumetier, Baptiste, Boutanquoi, Pierre-Marie, Droin, Nathalie, Kayaci, Cémile, Cartier, Jessy, Gemble, Simon, Marcion, Guillaume, Gonzalez, Daniel, Boidot, Romain, Garrido, Carmen, Micheau, Olivier, Solary, Eric, and Dubrez, Laurence

Published
2018
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6. Radiotheranostic Agents in Hematological Malignancies

Author

Caers, Jo, primary, Duray, Elodie, additional, Vrancken, Louise, additional, Marcion, Guillaume, additional, Bocuzzi, Valentina, additional, De Veirman, Kim, additional, Krasniqi, Ahmet, additional, Lejeune, Margaux, additional, Withofs, Nadia, additional, Devoogdt, Nick, additional, Dumoulin, Mireille, additional, Karlström, Amelie Eriksson, additional, and D’Huyvetter, Matthias, additional

Published
2022
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7. Restoring Anticancer Immune Response by Targeting Tumor-Derived Exosomes With a HSP70 Peptide Aptamer

Author

Gobbo, Jessica, Marcion, Guillaume, Cordonnier, Marine, Dias, Alexandre M. M., Pernet, Nicolas, Hammann, Arlette, Richaud, Sarah, Mjahed, Hajare, Isambert, Nicolas, Clausse, Victor, Rébé, Cédric, Bertaut, Aurélie, Goussot, Vincent, Lirussi, Frédéric, Ghiringhelli, François, de Thonel, Aurélie, Fumoleau, Pierre, Seigneuric, Renaud, and Garrido, Carmen

Published
2016
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8. Radiotheranostic Agents in Hematological Malignancies

Author

Caers, Jo, Duray, Elodie, Vrancken, Louise, Marcion, Guillaume, Bocuzzi, Valentina, De Veirman, Kim, Krasniqi, Ahmet, Lejeune, Margaux, Withofs, Nadia, Devoogdt, Nick, Dumoulin, Mireille, Eriksson Karlström, Amelie, D'Huyvetter, Matthias, Caers, Jo, Duray, Elodie, Vrancken, Louise, Marcion, Guillaume, Bocuzzi, Valentina, De Veirman, Kim, Krasniqi, Ahmet, Lejeune, Margaux, Withofs, Nadia, Devoogdt, Nick, Dumoulin, Mireille, Eriksson Karlström, Amelie, and D'Huyvetter, Matthias

Abstract

Radioimmunotherapy (RIT) is a cancer treatment that combines radiation therapy with tumor-directed monoclonal antibodies (Abs). Although RIT had been introduced for the treatment of CD20 positive non-Hodgkin lymphoma decades ago, it never found a broad clinical application. In recent years, researchers have developed theranostic agents based on Ab fragments or small Ab mimetics such as peptides, affibodies or single-chain Abs with improved tumor-targeting capacities. Theranostics combine diagnostic and therapeutic capabilities into a single pharmaceutical agent; this dual application can be easily achieved after conjugation to radionuclides. The past decade has seen a trend to increased specificity, fastened pharmacokinetics, and personalized medicine. In this review, we discuss the different strategies introduced for the noninvasive detection and treatment of hematological malignancies by radiopharmaceuticals. We also discuss the future applications of these radiotheranostic agents.

Published
2022
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10. HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia

Author

Arlet, Jean-Benoit, Ribeil, Jean-Antoine, Guillem, Flavia, Negre, Olivier, Hazoume, Adonis, Marcion, Guillaume, Beuzard, Yves, Dussiot, Michael, Moura, Ivan Cruz, Demarest, Samuel, de Beauchene, Isaure Chauvot, Belaid-Choucair, Zakia, Sevin, Margaux, Madel, Thiago Trovati, Auclair, Christian, Leboulch, Philippe, Chretien, Stany, Tchertanov, Luba, Baudin-Creuza, Veronique, Seigneuric, Renaud, Fontenay, Michaela, Garrido, Carmen, Hermine, Olivier, and Courtois, Genevieve

Subjects
Hemoglobin -- Health aspects, Heat shock proteins -- Physiological aspects -- Research, Apoptosis -- Physiological aspects, Thalassemia -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

β-Thalassaemia major (β-TM) is an inherited haemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of haemoglobin, leading to the accumulation of free α-globin chains that form toxic aggregates (1,2). Despite extensive knowledge of the molecular defects causing β-TM, little is known of the mechanisms responsible for the ineffective erythropoiesis observed in the condition, which is characterized by accelerated erythroid differentiation, maturation arrest and apoptosis at the polychromatophilic stage (3-6). We have previously demonstrated that normal human erythroid maturation requires a transient activation of caspase-3 at the later stages of maturation (7). Although erythroid transcription factor GATA-1, the master transcriptional factor of erythropoiesis, is a caspase-3 target, it is not cleaved during erythroid differentiation. We have shown that, in human erythroblasts, the chaperone heat shock protein70 (HSP70) is constitutively expressed and, at later stages of maturation, translocates into the nucleus and protects GATA-1 from caspase-3 cleavage (8). The primary role of this ubiquitous chaperone is to participate in the refolding of proteins denatured by cytoplasmic stress, thus preventing their aggregation (9). Here we show in vitro that during the maturation of human β-TM erythroblasts, HSP70 interacts directly with free α-globin chains. As a consequence, HSP70 is sequestrated in the cytoplasm and GATA-1 is no longer protected, resulting in end-stage maturation arrest and apoptosis. Transduction of a nuclear-targeted HSP70 mutant or a caspase-3-uncleavable GAT A-1 mutant restores terminal maturation of β-TM erythroblasts, which may provide a rationale for new targeted therapies of β-TM., To investigate the hypothesis that HSP70 can be sequestrated in the cytoplasm of mature β-TM erythroblasts by binding to free α-globin chains of haemoglobin or aggregates, we analysed its subcellular [...]

Published
2014

11. Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore

Author

Privat, Malorie, primary, Bellaye, Pierre-Simon, additional, Lescure, Robin, additional, Massot, Aurélie, additional, Baffroy, Océane, additional, Moreau, Mathieu, additional, Racoeur, Cindy, additional, Marcion, Guillaume, additional, Denat, Franck, additional, Bettaieb, Ali, additional, Collin, Bertrand, additional, Bodio, Ewen, additional, Paul, Catherine, additional, and Goze, Christine, additional

Published
2021
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13. Nanofitins targeting heat shock protein 110: An innovative immunotherapeutic modality in cancer

Author

Marcion, Guillaume, primary, Hermetet, François, additional, Neiers, Fabrice, additional, Uyanik, Burhan, additional, Dondaine, Lucile, additional, Dias, Alexandre M. M., additional, Da Costa, Laurène, additional, Moreau, Mathieu, additional, Bellaye, Pierre‐Simon, additional, Collin, Bertrand, additional, Gobbo, Jessica, additional, Briand, Loïc, additional, Seigneuric, Renaud, additional, Kitten, Olivier, additional, Cinier, Mathieu, additional, and Garrido, Carmen, additional

Published
2021
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14. XPO1 regulates erythroid differentiation and is a new target for the treatment of β-thalassemia

Author

Guillem, Flavia, Dussiot, Michael, Colin, Elia, Suriyun, Thunwarat, Arlet, Jean Benoit, Goudin, Nicolas, Marcion, Guillaume, Seigneuric, Renaud, Causse, Sebastien, Gonin, Patrick, Gastou, Marc, Deloger, Marc, Rossignol, Julien, Lamarque, Mathilde, Bellaid Choucair, Zakia, Gautier, Emilie Fleur, Ducamp, Sarah, Vandekerckhove, Julie, Moura, Ivan, Maciel, Thiago, Garrido, Carmen, An, Xiuli, Mayeux, Patrick, Mohandas, Narla, COURTOIS, genevieve, Hermine, Olivier, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme d'Imagerie Cellulaire [SFR Necker], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Institut Gustave Roussy (IGR), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Eléments transposables, évolution, populations, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Angiogénèse embryonnaire et pathologique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-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), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Red Cell Physiology Laboratory [New York, USA], New York Blood Center, Service d'hématolgie adulte, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Maladies Génétiques Imagine [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Centre interdisciplinaire de recherche en biologie (CIRB), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), COURTOIS, genevieve, and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, hemic and lymphatic diseases, Article, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

β-thalassemia major (β-TM) is an inherited hemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of hemoglobin, leading to the accumulation of free a-globin chains that aggregate and cause ineffective erythropoiesis. We have previously demonstrated that terminal erythroid maturation requires a transient activation of caspase-3 and that the chaperone Heat Shock Protein 70 (HSP70) accumulates in the nucleus to protect GATA-1 transcription factor from caspase-3 cleavage. This nuclear accumulation of HSP70 is inhibited in human β-TM erythroblasts due to HSP70 sequestration in the cytoplasm by free a-globin chains, resulting in maturation arrest and apoptosis. Likewise, terminal maturation can be restored by transduction of a nuclear-targeted HSP70 mutant. Here we demonstrate that in normal erythroid progenitors, HSP70 localization is regulated by the exportin-1 (XPO1), and that treatment of β-thalassemic erythroblasts with an XPO1 inhibitor increased the amount of nuclear HSP70, rescued GATA-1 expression and improved terminal differentiation, thus representing a new therapeutic option to ameliorate ineffective erythropoiesis of β-TM.

Published
2019

15. XPO1 regulates erythroid differentiation and is a new target for the treatment of β-thalassemia

Author

Guillem, Flavia, primary, Dussiot, Michaël, additional, Colin, Elia, additional, Suriyun, Thunwarat, additional, Arlet, Jean Benoit, additional, Goudin, Nicolas, additional, Marcion, Guillaume, additional, Seigneuric, Renaud, additional, Causse, Sebastien, additional, Gonin, Patrick, additional, Gastou, Marc, additional, Deloger, Marc, additional, Rossignol, Julien, additional, Lamarque, Mathilde, additional, Choucair, Zakia Belaid, additional, Gautier, Emilie Fleur, additional, Ducamp, Sarah, additional, Vandekerckhove, Julie, additional, Moura, Ivan C., additional, Maciel, Thiago Trovati, additional, Garrido, Carmen, additional, An, Xiuli, additional, Mayeux, Patrick, additional, Mohandas, Narla, additional, Courtois, Geneviève, additional, and Hermine, Olivier, additional

Published
2020
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16. TRIM33 prevents pulmonary fibrosis by impairing TGF-β1 signalling

Author

Boutanquoi, Pierre-Marie, primary, Burgy, Olivier, additional, Beltramo, Guillaume, additional, Bellaye, Pierre-Simon, additional, Dondaine, Lucile, additional, Marcion, Guillaume, additional, Pommerolle, Lenny, additional, Vadel, Aurélie, additional, Spanjaard, Maximilien, additional, Demidov, Oleg, additional, Mailleux, Arnaud, additional, Crestani, Bruno, additional, Kolb, Martin, additional, Garrido, Carmen, additional, Goirand, Françoise, additional, and Bonniaud, Philippe, additional

Published
2020
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18. Selecting the first chemical molecule inhibitor of HSP110 for colorectal cancer therapy

Author

Gozzi, Gustavo J., primary, Gonzalez, Daniel, additional, Boudesco, Christophe, additional, Dias, Alexandre M. M., additional, Gotthard, Guillaume, additional, Uyanik, Burhan, additional, Dondaine, Lucile, additional, Marcion, Guillaume, additional, Hermetet, François, additional, Denis, Camille, additional, Hardy, Laurianne, additional, Suzanne, Peggy, additional, Douhard, Romain, additional, Jego, Gaetan, additional, Dubrez, Laurence, additional, Demidov, Oleg N., additional, Neiers, Fabrice, additional, Briand, Loïc, additional, Sopková-de Oliveira Santos, Jana, additional, Voisin-Chiret, Anne-Sophie, additional, and Garrido, Carmen, additional

Published
2019
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19. HSP110 translocates to the nucleus upon genotoxic chemotherapy and promotes DNA repair in colorectal cancer cells

Author

Causse, Sebastien Z., primary, Marcion, Guillaume, additional, Chanteloup, Gaëtan, additional, Uyanik, Burhan, additional, Boudesco, Christophe, additional, Grigorash, Bogdan B., additional, Douhard, Romain, additional, Dias, Alexandre M. M., additional, Dumetier, Baptiste, additional, Dondaine, Lucile, additional, Gozzi, Gustavo J., additional, Moussay, Etienne, additional, Paggetti, Jérôme, additional, Mirjolet, Céline, additional, de Thonel, Aurélie, additional, Dubrez, Laurence, additional, Demidov, Oleg N., additional, Gobbo, Jessica, additional, and Garrido, Carmen, additional

Published
2018
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20. DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues

Author

Glorian, Valérie, Allègre, Jennifer, Berthelet, Jean, Dumetier, Baptiste, Boutanquoi, Pierre-Marie, Droin, Nathalie, Kayaci, Cémile, Cartier, Jessy, Gemble, Simon, Marcion, Guillaume, Gonzalez, Daniel, Boidot, Romain, Garrido, Carmen, Michaud, Olivier, Solary, Eric, Dubrez, Laurence, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématopoïèse normale et pathologique (U1170 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hématopoïèse normale et pathologique ( U1170 Inserm ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
endocrine system, Transcription, Genetic, polysialic acid, HDL, Ubiquitin-Protein Ligases, Arginine, Methylation, Inhibitor of Apoptosis Proteins, S Phase, LDL, Mice, Structure-Activity Relationship, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Animals, Humans, hypothalamus, Polyubiquitin, synaptic plasticity, Protein Stability, Lysine, Ubiquitination, Correction, Original Article, biological phenomena, cell phenomena, and immunity, atherosclerosis, E2F1 Transcription Factor, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, DNA Damage
Abstract

IF 5.965; International audience; The E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control. Importantly, E2F1 stabilization in response to etoposide-induced DNA damage or during the S phase of cell cycle, as revealed by cyclin A silencing, is associated with K63-poly-ubiquitinylation of E2F1 on lysine 161/164 residues and involves cIAP1. Our results reveal an additional level of regulation of the stability and the activity of E2F1 by a non-degradative K63-poly-ubiquitination and uncover a novel function for the E3-ubiquitin ligase cIAP1.

Published
2017

21. N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death : N-glycosylation of TRAIL receptors

Author

Dufour, Florent, Rattier, Thibault, Shirley, Sarah, Picarda, Gaelle, Constantinescu, Andrei Alexandru, Morlé, Aymeric, Zakaria, Al Batoul, Marcion, Guillaume, Causse, Sebastien, Szegezdi, eva, Zajonc, Dirk Michael, Seigneuric, Renaud, Guichard, Gilles, Gharbi, Tijani, Picaud, Fabien, Herlem, Guillaume, Garrido, Carmen, Schneider, Pascal, Benedict, Chris Alan, Micheau, Olivier, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe HSPpathies (LNC - U1231), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), La Jolla Institute for Allergy & Immunology ( LA JOLLA Institute ), Nanomédecine, imagerie, thérapeutique - UFC ( NIT / NANOMEDECINE ), Université de Franche-Comté ( UFC ) -Université Bourgogne Franche-Comté ( UBFC ), Apoptosis Research Centre [Galway, Ireland] ( ARC ), National University of Ireland [Galway] ( NUI Galway ), Ghent University [Belgium] ( UGENT ), Chimie et Biologie des Membranes et des Nanoobjets ( CBMN ), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux ( ENITAB ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut de Biochimie, Université de Lausanne ( UNIL ), INCa, ARC, Ligue Nationale Contre le Cancer, Swiss National Science Foundation, National Institute of Health (AI117530 and AI101423), Conseil Regional de Bourgogne, Ministère de la recherche, ANR : Labex,LipSTIC,ANR-11-LABX-0021-01-LipSTIC, ANR-07-PCVI-0031,ApoMULTI-LIB,A multivalent peptide library approach to identify functional TRAIL mimetics ( 2007 ), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, La Jolla Institute for Allergy & Immunology (LA JOLLA Institute), Nanomédecine, imagerie, thérapeutique - UFC (EA 4662) (NIT / NANOMEDECINE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), Apoptosis Research Centre [Galway, Ireland] (ARC), National University of Ireland [Galway] (NUI Galway), Ghent University [Belgium] (UGENT), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Université de Lausanne (UNIL), ANR: 11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), ANR-07-PCVI-0031,ApoMULTI-LIB,A multivalent peptide library approach to identify functional TRAIL mimetics(2007), La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Universiteit Gent = Ghent University [Belgium] (UGENT), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, and ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011)

Subjects
TRAIL-R2, TNF, apoptosis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, TRAIL, DR4, TRAIL-R1, N-glycosylation, DR5, signaling, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract

International audience; APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.

Published
2017

22. Serum Gp96 is a chaperone of complement-C3 during graft-versus-host disease

Author

Seignez, Antoine, primary, Joly, Anne-Laure, additional, Chaumonnot, Killian, additional, Hazoumé, Adonis, additional, Sanka, Michel, additional, Marcion, Guillaume, additional, Boudesco, Christophe, additional, Hammann, Arlette, additional, Seigneuric, Renaud, additional, Jégo, Gaetan, additional, Ducoroy, Patrick, additional, Delarue, Patrice, additional, Senet, Patrick, additional, Castilla-Llorente, Cristina, additional, Solary, Eric, additional, Durey, Marie-Agnès, additional, Rubio, Marie-Thérèse, additional, Hermine, Olivier, additional, Kohli, Evelyne, additional, and Garrido, Carmen, additional

Published
2017
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23. XPO1 (Exportin-1) Is a Major Regulator of Human Erythroid Differentiation. Potential Clinical Applications to Decrease Ineffective Erythropoiesis of Beta-Thalassemia

Author

Guillem, Flavia, primary, Dussiot, Michael, additional, Causse, Sebastien, additional, Marcion, Guillaume, additional, Gautier, Emilie-Fleur, additional, Rossignol, Julien, additional, Arlet, Jean benoit, additional, Lamarque, Mathilde, additional, Mayeux, Patrick, additional, Verdier, Frederique, additional, An, Xiuli, additional, Ribeil, Jean-Antoine, additional, Garrido, Carmen, additional, Courtois, Genevieve, additional, Mohandas, Narla, additional, and Hermine, Olivier, additional

Published
2015
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24. Restoring Anticancer Immune Response by Targeting Tumor-Derived Exosomes With a HSP70 Peptide Aptamer

Author

Gobbo, Jessica, primary, Marcion, Guillaume, additional, Cordonnier, Marine, additional, Dias, Alexandre M. M., additional, Pernet, Nicolas, additional, Hammann, Arlette, additional, Richaud, Sarah, additional, Mjahed, Hajare, additional, Isambert, Nicolas, additional, Clausse, Victor, additional, Rébé, Cédric, additional, Bertaut, Aurélie, additional, Goussot, Vincent, additional, Lirussi, Frédéric, additional, Ghiringhelli, François, additional, de Thonel, Aurélie, additional, Fumoleau, Pierre, additional, Seigneuric, Renaud, additional, and Garrido, Carmen, additional

Published
2015
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26. Patients With Colorectal Tumors With Microsatellite Instability and Large Deletions in HSP110 T17 Have Improved Response to 5-Fluorouracil–Based Chemotherapy

Author

Collura, Ada, primary, Lagrange, Anaïs, additional, Svrcek, Magali, additional, Marisa, Laetitia, additional, Buhard, Olivier, additional, Guilloux, Agathe, additional, Wanherdrick, Kristell, additional, Dorard, Coralie, additional, Taieb, Anna, additional, Saget, Arnaud, additional, Loh, Marie, additional, Soong, Richie, additional, Zeps, Nikolajs, additional, Platell, Cameron, additional, Mews, Andrew, additional, Iacopetta, Barry, additional, De Thonel, Aurélie, additional, Seigneuric, Renaud, additional, Marcion, Guillaume, additional, Chapusot, Caroline, additional, Lepage, Come, additional, Bouvier, Anne–Marie, additional, Gaub, Marie–Pierre, additional, Milano, Gérard, additional, Selves, Janick, additional, Senet, Patrick, additional, Delarue, Patrice, additional, Arzouk, Hayat, additional, Lacoste, Claire, additional, Coquelle, Arnaud, additional, Bengrine–Lefèvre, Leila, additional, Tournigand, Christophe, additional, Lefèvre, Jérémie H., additional, Parc, Yann, additional, Biard, Denis S., additional, Fléjou, Jean–François, additional, Garrido, Carmen, additional, and Duval, Alex, additional

Published
2014
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27. Dose-dependent biphasic leptin-induced proliferation is caused by non-specific IL-6/ NF-κB pathway activation in human myometrial cells.

Author

Barrichon, Marina, Hadi, Tarik, Wendremaire, Maeva, Ptasinski, Clémentine, Seigneuric, Renaud, Marcion, Guillaume, Delignette, Marc, Marchet, Jacques, Dumas, Monique, Sagot, Paul, Bardou, Marc, Garrido, Carmen, and Lirussi, Frédéric

Subjects
INTERLEUKINS, NF-kappa B, SMOOTH muscle, CELL proliferation, LEPTIN receptors, OVERWEIGHT women, PARTURITION, DURATION of pregnancy, DISEASES
Abstract

Background and Purpose Leptin, an adipokine synthesized by the placenta during pregnancy, has been proposed for the management of preterm labour ( PTL), as it is able to prevent in vitro uterine contractility and remodelling associated with labour onset. Another common feature of labour onset is the phenotypic switch of myometrial smooth muscle cells from a proliferative to a hypertrophic state. As proliferative effects have been demonstrated for leptin in other tissues, we aimed to investigate its ability to induce myometrial proliferation and thus to maintain uterine quiescence. Experimental Approach We stimulated human primary myometrial smooth muscle cells with leptin in the presence or absence of receptor antagonists or signalling pathway inhibitors. Key Results Leptin induced myometrial cell proliferation in a biphasic manner. At 6.25 ng·mL−1, leptin-induced proliferation was mediated by the leptin receptor and required the early activation of ERK1/2. At a concentration above 25 ng·mL−1, leptin induced direct non-specific stimulation of the IL-6 receptor, leading to NF-κB activation, and exerted anti-proliferative effects. However, at 50 ng·mL−1, leptin re-induces proliferation via IL-6 receptor stimulation that requires STAT3 and delayed ERK1/2 activation. Conclusions and Implications These data bring new insights into leptin signalling-induced myometrial proliferation and its interrelationship with the IL-6/ IL-6 receptor axis. In the light of our previous work, the present study emphasizes the potential value of leptin in the pharmacological management of PTL and it also strengthens the hypothesis that leptin might be a contributory factor in the parturition-related disorders observed in obese women. [ABSTRACT FROM AUTHOR]

Published
2015
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29. Patients With Colorectal Tumors With Microsatellite Instability and Large Deletions in HSP110 T17 Have Improved Response to 5-Fluorouracil–Based Chemotherapy.

Author

Collura, Ada, Lagrange, Anaïs, Svrcek, Magali, Marisa, Laetitia, Buhard, Olivier, Guilloux, Agathe, Wanherdrick, Kristell, Dorard, Coralie, Taieb, Anna, Saget, Arnaud, Loh, Marie, Soong, Richie, Zeps, Nikolajs, Platell, Cameron, Mews, Andrew, Iacopetta, Barry, De Thonel, Aurélie, Seigneuric, Renaud, Marcion, Guillaume, and Chapusot, Caroline

Abstract

Background & Aims: Patients with colorectal tumors with microsatellite instability (MSI) have better prognoses than patients with tumors without MSI, but have a poor response to 5-fluorouracil–based chemotherapy. A dominant-negative form of heat shock protein (HSP)110 (HSP110DE9) expressed by cancer cells with MSI, via exon skipping caused by somatic deletions in the T17 intron repeat, sensitizes the cells to 5-fluorouracil and oxaliplatin. We investigated whether HSP110 T17 could be used to identify patients with colorectal cancer who would benefit from adjuvant chemotherapy with 5-fluorouracil and oxaliplatin. Methods: We characterized the interaction between HSP110 and HSP110DE9 using surface plasmon resonance. By using polymerase chain reaction and fragment analysis, we examined how the size of somatic allelic deletions in HSP110 T17 affected the HSP110 protein expressed by tumor cells. We screened 329 consecutive patients with stage II–III colorectal tumors with MSI who underwent surgical resection at tertiary medical centers for HSP110 T17. Results: HSP110 and HSP110DE9 interacted in a 1:1 ratio. Tumor cells with large deletions in T17 had increased ratios of HSP110DE9:HSP110, owing to the loss of expression of full-length HSP110. Deletions in HSP110 T17 were mostly biallelic in primary tumor samples with MSI. Patients with stage II–III cancer who received chemotherapy and had large HSP110 T17 deletions (≥5 bp; 18 of 77 patients, 23.4%) had longer times of relapse-free survival than patients with small or no deletions (≤4 bp; 59 of 77 patients, 76.6%) in multivariate analysis (hazard ratio, 0.16; 95% confidence interval, 0.012–0.8; P = .03). We found a significant interaction between chemotherapy and T17 deletion (P = .009). Conclusions: About 25% of patients with stages II–III colorectal tumors with MSI have an excellent response to chemotherapy, due to large, biallelic deletions in the T17 intron repeat of HSP110 in tumor DNA. [Copyright &y& Elsevier]

Published
2014
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30. DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues.

Author

Glorian V, Allègre J, Berthelet J, Dumetier B, Boutanquoi PM, Droin N, Kayaci C, Cartier J, Gemble S, Marcion G, Gonzalez D, Boidot R, Garrido C, Michaud O, Solary E, and Dubrez L

Subjects
Animals, Arginine metabolism, Humans, Methylation, Mice, Protein Stability, Structure-Activity Relationship, Transcription, Genetic, DNA Damage, E2F1 Transcription Factor metabolism, Inhibitor of Apoptosis Proteins metabolism, Lysine metabolism, Polyubiquitin metabolism, S Phase, Ubiquitin-Protein Ligases metabolism, Ubiquitination
Abstract

The E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control. Importantly, E2F1 stabilization in response to etoposide-induced DNA damage or during the S phase of cell cycle, as revealed by cyclin A silencing, is associated with K63-poly-ubiquitinylation of E2F1 on lysine 161/164 residues and involves cIAP1. Our results reveal an additional level of regulation of the stability and the activity of E2F1 by a non-degradative K63-poly-ubiquitination and uncover a novel function for the E3-ubiquitin ligase cIAP1.

Published
2017
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31. N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.

Author

Dufour F, Rattier T, Shirley S, Picarda G, Constantinescu AA, Morlé A, Zakaria AB, Marcion G, Causse S, Szegezdi E, Zajonc DM, Seigneuric R, Guichard G, Gharbi T, Picaud F, Herlem G, Garrido C, Schneider P, Benedict CA, and Micheau O

Subjects
Amino Acid Sequence, Animals, Cell Line, Cytomegalovirus metabolism, Glycosylation, HCT116 Cells, Humans, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Mice, Mutagenesis, Site-Directed, Nanoparticles chemistry, Receptors, TNF-Related Apoptosis-Inducing Ligand deficiency, Receptors, TNF-Related Apoptosis-Inducing Ligand genetics, Sequence Alignment, Tunicamycin toxicity, Viral Proteins genetics, Viral Proteins metabolism, Apoptosis drug effects, Receptors, TNF-Related Apoptosis-Inducing Ligand metabolism, TNF-Related Apoptosis-Inducing Ligand toxicity
Abstract

APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.

Published
2017
Full Text
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