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Your search keyword '"4E-BP1 phosphorylation"' showing total 3 results
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3 results on '"4E-BP1 phosphorylation"'

1. Functional interaction between RAFT1/FRAP/mTOR and protein kinase Cd in the regulation of cap-dependent initiation of translation.

Author

Kumar, Vijay, Pandey, Pramod, Sabatini, David, Kumar, Madhur, Majumder, Pradip K., Bharti, Ajit, Carmichael, Gordon, Kufe, Donald, and Kharbanda, Surender

Subjects
*PHOSPHORYLATION, *GROWTH factors, *HORMONE synthesis, *PROTEINS, *IMMUNOSUPPRESSIVE agents, *PEPTIDES
Abstract

Hormones and growth factors induce protein translation in part by phosphorylation of the eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). The rapamycin and FK506-binding protein (FKBP)-target 1 (RAFT1, also known as FRAP) is a mammalian homolog of the Saccharomyces cerevisiae target of rapamycin proteins (mTOR) that regulates 4E-BP1. However, the molecular mechanisms involved in growth factor-initiated phosphorylation of 4E-BP1 are not well understood. Here we demonstrate that protein kinase Cδ (PKCδ) associates with RAFT1 and that PKCδ is required for the phosphorylation and inactivation of 4E-BP1. PKCδ-mediated phosphorylation of 4E-BP1 is wortmannin resistant but rapamycin sensitive. As shown for serum, phosphorylation of 4E-BP1 by PKCδ inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation. Moreover, a dominant-negative mutant of PKCδ inhibits serum-induced phosphorylation of 4E-BP1. These findings demonstrate that PKCδ associates with RAFT1 and thereby regulates phosphorylation of 4E-BP1 and cap-dependent initiation of protein translation. [ABSTRACT FROM AUTHOR]

Published
2000
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2. Hepatitis C virus core protein targets 4E-BP1 expression and phosphorylation and potentiates Myc-induced liver carcinogenesis in transgenic mice

Author

Abdallah, Cosette, Lejamtel, Charlène, Benzoubir, Nassima, Battaglia, Serena, Sidahmed-Adrar, Nazha, Desterke, Christophe, Lemasson, Matthieu, Rosenberg, Arielle R., Samuel, Didier, Bréchot, Christian, Pflieger, Delphine, Le Naour, François, Bourgeade, Marie-Françoise, Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement (LAMBE - UMR 8587), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut André Lwoff, Unité de service de l'Institut André Lwoff (US 33 Inserm), AP-HP Hôpital Paul Brousse [Paris]-Institut André Lwoff [Villejuif] (IAL), Virologie de l'hépatite C (EA 4474), Université Paris Descartes - Paris 5 (UPD5), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Universitaire de la Francophonie (AUF), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Paul Brousse, Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université d'Évry-Val-d'Essonne (UEVE)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement (LAMBE), Université Paris-Seine-Université Paris-Seine-Université d'Évry-Val-d'Essonne (UEVE)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Saclay (COmUE), Unité mixte de service UMS33 [Institut André Lwoff] (UMS33 Inserm/IAL), Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut André Lwoff [Villejuif] (IAL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Etude de la dynamique des protéomes (EDyP ), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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), Hôpital Paul Brousse-Institut André Lwoff [Villejuif] (IAL), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11)

Subjects
mitogen activated protein kinase p38, host cell, gene amplification, complementary DNA, animal cell, SILAC, initiation factor 4E binding protein 1, vimentin, hepatocellular carcinoma cell line, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Huh-7 cell line, membrane protein, insulin receptor, 4E-BP1 phosphorylation, Hermes antigen, quantitative analysis, Hepatitis C virus, liver cell, virus diseases, phosphoproteomics, hepatocellular carcinoma, unclassified drug, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, tumor growth, liver carcinogenesis, protein transport, transcription regulation, signal transduction, in vitro study, animal experiment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, cancer growth, animal tissue, in vivo study, HCV core, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], core protein, controlled study, human, protein expression, mouse, nonhuman, protein MTA1, RNA translation, animal model, human cell, intracellular signaling, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, protein phosphorylation, transgenic mouse, validation process, initiation factor 4E, Myc protein, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], upregulation
Abstract

International audience; Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation. Among the eukaryotic initiation factors that govern the translational machinery, 4E-BP1 represents a master regulator of protein synthesis that is associated with the development and progression of cancers due to its ability to increase protein expression of oncogenic pathways. Enhanced levels of 4E-BP1 in non-modified and phosphorylated forms were validated in human hepatoma cells and in mouse primary hepatocytes expressing HCV core, in the livers of HCV core transgenic mice as well as in HCV-infected human primary hepatocytes. The contribution of HCV core in carcinogenesis and the status of 4E-BP1 expression and phosphorylation were studied in HCV core/ Myc double transgenic mice. HCV core increased the levels of 4E-BP1 expression and phosphorylation and significantly accelerated the onset of Myc-induced tumorigenesis in these double transgenic mice. These results reveal a novel function of HCV core in liver carcinogenesis potentiation. They position 4E-BP1 as a tumor-specific target of HCV core and support the involvement of the 4E-BP1/eIF4E axis in hepatocarcinogenesis.

Published
2017
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3. Hepatitis C virus core protein targets 4E-BP1 expression and phosphorylation and potentiates Myc-induced liver carcinogenesis in transgenic mice.

Author

Abdallah C, Lejamtel C, Benzoubir N, Battaglia S, Sidahmed-Adrar N, Desterke C, Lemasson M, Rosenberg AR, Samuel D, Bréchot C, Pflieger D, Le Naour F, and Bourgeade MF

Abstract

Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation. Among the eukaryotic initiation factors that govern the translational machinery, 4E-BP1 represents a master regulator of protein synthesis that is associated with the development and progression of cancers due to its ability to increase protein expression of oncogenic pathways. Enhanced levels of 4E-BP1 in non-modified and phosphorylated forms were validated in human hepatoma cells and in mouse primary hepatocytes expressing HCV core, in the livers of HCV core transgenic mice as well as in HCV-infected human primary hepatocytes. The contribution of HCV core in carcinogenesis and the status of 4E-BP1 expression and phosphorylation were studied in HCV core/Myc double transgenic mice. HCV core increased the levels of 4E-BP1 expression and phosphorylation and significantly accelerated the onset of Myc-induced tumorigenesis in these double transgenic mice. These results reveal a novel function of HCV core in liver carcinogenesis potentiation. They position 4E-BP1 as a tumor-specific target of HCV core and support the involvement of the 4E-BP1/eIF4E axis in hepatocarcinogenesis., Competing Interests: CONFLICTS OF INTEREST All authors have nothing to disclose.

Published
2017
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