The Retinoblastoma-Histone Deacetylase 3 Complex Inhibits PPARγ and Adipocyte Differentiation

AbstractThe 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 γ (PPARγ), a nuclear receptor pivotal for adipogenesis, promotes adipocyte differentiation more efficiently in the absence of RB. PPARγ and RB were shown to coimmunoprecipitate, and this PPARγ-RB complex also contains the histone deacetylase HDAC3, thereby attenuating PPARγ's capacity to drive gene expression and adipocyte differentiation. Dissociation of the PPARγ-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 PPARγ activity and adipocyte differentiation