The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation.
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.
Fajas
Lluis
L
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France.
Egler
Viviane
V
Reiter
Raphael
R
Hansen
Jacob
J
Kristiansen
Karsten
K
Debril
Marie-Bernard
MB
Miard
Stéphanie
S
Auwerx
Johan
J
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
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