1. Cyclin G2 regulates adipogenesis through PPAR gamma coactivation
- Author
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Aguilar, Victor, Annicotte, Jean-Sébastien, Escote, Xavier, Vendrell, Joan, Langin, Dominique, Fajas, Lluis, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Endocrinology and Diabetes Unit, University Hospital of Tarragona, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants from FRM, INCA, and ANR., and Le Ster, Yves
- Subjects
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,PPARγ ,MESH: Immunoprecipitation ,MESH: Transfection ,MESH: Cyclin G2 ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,MESH: 3T3-L1 Cells ,MESH: Male ,adipogenesis ,MESH: PPAR gamma ,MESH: Mice, Inbred C57BL ,MESH: Reverse Transcriptase Polymerase Chain Reaction ,MESH: Up-Regulation ,cyclin G2 ,MESH: Animals ,MESH: Adipogenesis ,MESH: Fluorescent Antibody Technique ,MESH: Mice ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,MESH: Adipocytes ,MESH: Cells, Cultured - Abstract
International audience; Cell cycle regulators such as cyclins, cyclin-dependent kinases, or retinoblastoma protein play important roles in the differentiation of adipocytes. In the present paper, we investigated the role of cyclin G2 as a positive regulator of adipogenesis. Cyclin G2 is an unconventional cyclin which expression is up-regulated during growth inhibition or apoptosis. Using the 3T3-F442A cell line, we observed an up-regulation of cyclin G2 expression at protein and mRNA levels throughout the process of cell differentiation, with a further induction of adipogenesis when the protein is transiently overexpressed. We show here that the positive regulatory effects of cyclin G2 in adipocyte differentiation are mediated by direct binding of cyclin G2 to peroxisome proliferator-activated receptor γ (PPARγ), the key regulator of adipocyte differentiation. The role of cyclin G2 as a novel PPARγ coactivator was further demonstrated by chromatin immunoprecipitation assays, which showed that the protein is present in the PPARγ-responsive element of the promoter of aP2, which is a PPARγ target gene. Luciferase reporter gene assays, showed that cyclin G2 positively regulates the transcriptional activity of PPARγ. The role of cyclin G2 in adipogenesis is further underscored by its increased expression in mice fed a high-fat diet. Taken together, our results demonstrate a novel role for cyclin G2 in the regulation of adipogenesis.
- Published
- 2010
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