Cyclin D3 Promotes Adipogenesis through Activation of Peroxisome Proliferator-Activated Receptor γ

Autor: Said Assou, Lluis Fajas, Anna Abella, Irena Iankova, Stéphanie Miard, David Sarruf
Přispěvatelé: Le Ster, Yves, Endocrinologie moléculaire et cellulaire des cancers, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants from INSERM (Avenir), FRM, Alfediam, and ARC. Anna Abella is supported by an Inserm Poste Vert grant, and Irena Iankova is supported by La Ligue National Contre le Cancer PhD fellowship. David Sarruf is supported by the Boehringer Ingelheim Fonds PhD scholarship program.
Rok vydání: 2005
Předmět:
Time Factors
Transcription
Genetic
Cyclin D
Cyclin A
Cyclin B
Gene Expression
Peroxisome proliferator-activated receptor
Mice
Chlorocebus aethiops
Adipocytes
Insulin
MESH: Animals
Cyclin D3
RNA
Small Interfering
MESH: Immunop
Cyclin
Mice
Knockout
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
MESH: Chromatin Immunoprecipitation
chemistry.chemical_classification
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
MESH: Gene Expression Regulation
Cyclin-Dependent Kinases
Up-Regulation
MESH: COS Cells
MESH: Cyclin-Dependent Kinases
Adipogenesis
COS Cells
Plasmids
MESH: Cyclin-Dependent Kinase 6
Chromatin Immunoprecipitation
MESH: Azo Compounds
Blotting
Western
Biology
Cell Line
MESH: Diet
Cyclins
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Animals
Immunoprecipitation
MESH: Blotting
Northern
MESH: Blotting
Western
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Obesity
Molecular Biology
MESH: Adipocytes
Cyclin-Dependent Kinase 6
Cell Biology
Blotting
Northern
MESH: Cyclins
MESH: Cercopithecus aethiops
Diet
MESH: Cell Line
PPAR gamma
Gene Expression Regulation
Microscopy
Fluorescence
chemistry
Mutation
NIH 3T3 Cells
biology.protein
Cancer research
Azo Compounds
Cyclin A2
Zdroj: Molecular and Cellular Biology
Molecular and Cellular Biology, 2005, 25 (22), pp.9985-95. ⟨10.1128/MCB.25.22.9985-9995.2005⟩
ISSN: 1098-5549
0270-7306
Popis: In addition to their role in cell cycle progression, new data reveal an emerging role of D-type cyclins in transcriptional regulation and cellular differentiation processes. Using 3T3-L1 cell lines to study adipogenesis, we observed an up-regulation of cyclin D3 expression throughout the differentiation process. Surprisingly, cyclin D3 was only minimally expressed during the initial stages of adipogenesis, when mitotic division is prevalent. This seemingly paradoxical expression led us to investigate a potential cell cycle-independent role for cyclin D3 during adipogenesis. We show here a direct interaction between cyclin D3 and the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). Our experiments reveal cyclin D3 acts as a ligand-dependent PPARgamma coactivator, which, together with its cyclin-dependent kinase partner, phosphorylates the A-B domain of the nuclear receptor. Overexpression and knockdown studies with cyclin D3 had marked effects on PPARgamma activity and subsequently on adipogenesis. Chromatin immunoprecipitation assays confirm the participation of cyclin D3 in the regulation of PPARgamma target genes. We show that cyclin D3 mutant mice are protected from diet-induced obesity, display smaller adipocytes, have reduced adipogenic gene expression, and are insulin sensitive. Our results indicate that cyclin D3 is an important factor governing adipogenesis and obesity.
Databáze: OpenAIRE
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