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

TY - JOUR

T1 - The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation

AU - Fajas, Lluis

AU - Egler, Viviane

AU - Reiter, Raphael

AU - Hansen, Jacob

AU - Kristiansen, Karsten

AU - Debril, Marie-Bernard

AU - Miard, Stéphanie

AU - Auwerx, Johan

N1 - Keywords: 3T3 Cells; Adipocytes; Animals; Cell Differentiation; Gene Expression Regulation, Enzymologic; Genes, Reporter; Histone Deacetylases; Lipoprotein Lipase; Macromolecular Substances; Mice; Phosphorylation; Protein Binding; Protein Structure, Tertiary; RNA, Messenger; Receptors, Cytoplasmic and Nuclear; Recombinant Fusion Proteins; Retinoblastoma Protein; Signal Transduction; Stem Cells; Thiazoles; Thiazolidinediones; Transcription Factors

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 12479814

SN - 1534-5807

VL - 3

SP - 903

EP - 910

JO - Developmental Cell

JF - Developmental Cell

IS - 6

ER -