TY - JOUR
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 -