The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation

Dev Cell. 2002 Dec;3(6):903-10. doi: 10.1016/s1534-5807(02)00360-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / enzymology*
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / genetics
  • Genes, Reporter / genetics
  • Histone Deacetylases / metabolism*
  • Lipoprotein Lipase / genetics
  • Lipoprotein Lipase / metabolism
  • Macromolecular Substances
  • Mice
  • Phosphorylation
  • Protein Binding / drug effects
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Recombinant Fusion Proteins
  • Retinoblastoma Protein / deficiency*
  • Retinoblastoma Protein / genetics
  • Rosiglitazone
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / enzymology*
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / metabolism*

Substances

  • Macromolecular Substances
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Retinoblastoma Protein
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Rosiglitazone
  • Lipoprotein Lipase
  • Histone Deacetylases
  • histone deacetylase 3