Open AccessDiscrete Roles for Peroxisome Proliferator-Activated Receptor γ and Retinoid X Receptor in Recruiting Nuclear Receptor Coactivators
Author(s) -
Wen Yang,
Christophe Rachez,
Leonard P. Freedman
Publication year - 2000
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.20.21.8008-8017.2000
Subject(s) - coactivator , transactivation , retinoid x receptor , nuclear receptor coactivator 1 , peroxisome proliferator activated receptor , nuclear receptor coactivator 2 , biology , nuclear receptor , retinoid x receptor alpha , microbiology and biotechnology , retinoid x receptor beta , biochemistry , receptor , transcription factor , gene
Peroxisome proliferator-activated receptor γ (PPARγ) plays a major role in adipogenesis. PPARγ binds to DNA as a heterodimer with retinoid X receptor (RXR), and PPARγ-RXR can be activated by ligands specific for either receptor; the presence of both ligands can result in a cooperative effect on the transactivation of target genes. How these ligands mediate transactivation, however, remains unclear. PPARγ is known to interact with both the p160/SRC-1 family of coactivators and the distinct, multisubunit coactivator complex called DRIP. A single DRIP subunit, DRIP205 (TRAP220, PBP), binds directly to PPARγ. Here we report that PPARγ and RXR selectively interacted with DRIP205 and p160 proteins in a ligand-dependent manner. At physiological concentrations, RXR-specific ligands only induced p160 binding to RXR, and PPARγ-specific ligands exclusively recruited DRIP205 but not p160 coactivators to PPARγ. This selectivity was not observed in interaction assays off DNA, implying that the specificity of coactivator binding in response to ligand is strongly influenced by the allosteric effects of DNA-bound heterodimers. These coactivator-selective effects were also observed in transient-transfection assays in the presence of overexpressed p160 or DRIP coactivators. The results suggest that the cooperative effects of PPARγ- and RXR-specific ligands may occur at the level of selective coactivator recruitment.