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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Adipocytes / cytology
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Adipocytes / drug effects
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Adipocytes / enzymology*
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Animals
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Enzymologic / genetics
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Genes, Reporter / genetics
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Histone Deacetylases / metabolism*
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Lipoprotein Lipase / genetics
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Lipoprotein Lipase / metabolism
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Macromolecular Substances
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Mice
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Phosphorylation
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Protein Binding / drug effects
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Protein Binding / genetics
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Protein Structure, Tertiary / genetics
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RNA, Messenger / metabolism
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Recombinant Fusion Proteins
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Retinoblastoma Protein / deficiency*
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Retinoblastoma Protein / genetics
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Rosiglitazone
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Stem Cells / cytology
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Stem Cells / drug effects
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Stem Cells / enzymology*
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Thiazoles / pharmacology
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Thiazolidinediones*
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Transcription Factors / metabolism*
Substances
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Macromolecular Substances
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Recombinant Fusion Proteins
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Retinoblastoma Protein
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Thiazoles
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Thiazolidinediones
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Transcription Factors
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Rosiglitazone
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Lipoprotein Lipase
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Histone Deacetylases
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histone deacetylase 3