The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Developmental Cell |
Volume | 3 |
Issue number | 6 |
Pages (from-to) | 903-10 |
Number of pages | 7 |
ISSN | 1534-5807 |
Publication status | Published - 2002 |
Bibliographical note
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
ID: 19664081