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

Lluis Fajas; Viviane Egler; Raphael Reiter; Jacob Hansen; Karsten Kristiansen; Marie-Bernard Debril; Stéphanie Miard; Johan Auwerx

doi:10.1016/S1534-5807(02)00360-X

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

Lluis Fajas, Viviane Egler, Raphael Reiter, Jacob Hansen, Karsten Kristiansen, Marie-Bernard Debril, Stéphanie Miard, Johan Auwerx

222 Citations (Scopus)

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 ¿ (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 language	English
Journal	Developmental Cell
Volume	3
Issue number	6
Pages (from-to)	903-910
ISSN	1534-5807
DOIs	https://doi.org/10.1016/S1534-5807(02)00360-X
Publication status	Published - 2002
Externally published	Yes

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title = "The Retinoblastoma-Histone Deacetylase 3 Complex Inhibits PPAR¿ and Adipocyte Differentiation",

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 ¿ (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.",

author = "Lluis Fajas and Viviane Egler and Raphael Reiter and Jacob Hansen and Karsten Kristiansen and Marie-Bernard Debril and St{\'e}phanie Miard and Johan Auwerx",

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doi = "10.1016/S1534-5807(02)00360-X",

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T1 - The Retinoblastoma-Histone Deacetylase 3 Complex Inhibits PPAR¿ 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

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 ¿ (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.

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 ¿ (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.

U2 - 10.1016/S1534-5807(02)00360-X

DO - 10.1016/S1534-5807(02)00360-X

M3 - Journal article

SN - 1534-5807

VL - 3

SP - 903

EP - 910

JO - Developmental Cell

JF - Developmental Cell

IS - 6

ER -

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

Abstract

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