title: The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation.
abstract: The retinoblastoma protein (RB) has previously been shown to facilitate adipocyte differentiation by inducing cell cycle arrest and enhancing the transactivation by the adipogenic CCAAT/enhancer binding proteins (C/EBP). We show here that the peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor pivotal for adipogenesis, promotes adipocyte differentiation more efficiently in the absence of RB. PPARgamma and RB were shown to coimmunoprecipitate, and this PPARgamma-RB complex also contains the histone deacetylase HDAC3, thereby attenuating PPARgamma's capacity to drive gene expression and adipocyte differentiation. Dissociation of the PPARgamma-RB-HDAC3 complex by RB phosphorylation or by inhibition of HDAC activity stimulates adipocyte differentiation. These observations underscore an important function of both RB and HDAC3 in fine-tuning PPARgamma activity and adipocyte differentiation.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France.
authors.forename: Lluis
authors.initials: L
authors.lastname: Fajas
authors.forename: Viviane
authors.initials: V
authors.lastname: Egler
authors.forename: Raphael
authors.initials: R
authors.lastname: Reiter
authors.forename: Jacob
authors.initials: J
authors.lastname: Hansen
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Marie-Bernard
authors.initials: MB
authors.lastname: Debril
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Miard
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006655:Histone Deacetylases / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein / Q000172:deficiency* / Q000235:genetics; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D008071:Lipoprotein Lipase; D046911:Macromolecular Substances; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000099186:Histone Deacetylase 3