The Retinoblastoma-Histone Deacetylase 3 Complex Inhibits PPAR¿ and Adipocyte Differentiation

Research output: Contribution to journalJournal articleResearchpeer-review

  • Lluis Fajas
  • Viviane Egler
  • Raphael Reiter
  • Jacob Hansen
  • Kristiansen, Karsten
  • Marie-Bernard Debril
  • Stéphanie Miard
  • Johan Auwerx
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 ¿ (PPAR¿), a nuclear receptor pivotal for adipogenesis, promotes adipocyte differentiation more efficiently in the absence of RB. PPAR¿ and RB were shown to coimmunoprecipitate, and this PPAR¿-RB complex also contains the histone deacetylase HDAC3, thereby attenuating PPAR¿'s capacity to drive gene expression and adipocyte differentiation. Dissociation of the PPAR¿-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 PPAR¿ activity and adipocyte differentiation.
Original languageEnglish
JournalDevelopmental Cell
Issue number6
Pages (from-to)903-910
Publication statusPublished - 2002
Externally publishedYes

ID: 14640168