Discrete roles for peroxisome proliferator-activated receptor γ and retinoid X receptor in recruiting nuclear receptor coactivators Journal Article


Authors: Yang, W.; Rachez, C.; Freedman, L. P.
Article Title: Discrete roles for peroxisome proliferator-activated receptor γ and retinoid X receptor in recruiting nuclear receptor coactivators
Abstract: 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.
Keywords: unclassified drug; human cell; nonhuman; binding affinity; animal cell; mouse; animal; mice; models, biological; protein protein interaction; cell line; protein binding; dose-response relationship, drug; transfection; transcription factors; gene activation; recombinant fusion proteins; carrier proteins; ligand; transactivation; glutathione transferase; ligands; dimerization; cell nucleus; cell nucleus receptor; vitamin d receptor; protein kinase; ligand binding; receptor binding; 3t3 cells; protein p160; allosterism; receptors, cytoplasmic and nuclear; receptor protein; receptors, retinoic acid; trans-activation (genetics); retinoid x receptor; human; priority journal; article; peroxisome proliferator activated receptor; support, u.s. gov't, p.h.s.; peroxisome proliferator activator receptor gamma; protein kinase p160; vitamin d3 receptor interacting protein
Journal Title: Molecular and Cellular Biology
Volume: 20
Issue: 21
ISSN: 0270-7306
Publisher: American Society for Microbiology  
Date Published: 2000-11-01
Start Page: 8008
End Page: 8017
Language: English
DOI: 10.1128/mcb.20.21.8008-8017.2000
PUBMED: 11027271
PROVIDER: scopus
PMCID: PMC86411
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Christophe Rachez
    17 Rachez
  2. Wen   Yang
    2 Yang