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PMID: 9584188 Published · ppublish English Journal Article

Transactivation by retinoid X receptor-peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimers: intermolecular synergy requires only the PPARgamma hormone-dependent activation function.

Molecular and cellular biology ·Vol. 18 ·No. 6 ·1998-06-00 ·Pages 3483-94

Schulman IG, Shao G, Heyman RA

Abstract

The ability of DNA sequence-specific transcription factors to synergistically activate transcription is a common property of genes transcribed by RNA polymerase II. The present work characterizes a unique form of intermolecular transcriptional synergy between two members of the nuclear hormone receptor superfamily. Heterodimers formed between peroxisome proliferator-activated receptor gamma (PPARgamma), an adipocyte-enriched member of the superfamily required for adipogenesis, and retinoid X receptors (RXRs) can activate transcription in response to ligands specific for either subunit of the dimer. Simultaneous treatment with ligands specific for both PPARgamma and RXR has a synergistic effect on the transactivation of reporter genes and on adipocyte differentiation in cultured cells. Mutation of the PPARgamma hormone-dependent activation domain (named tauc or AF-2) inhibits the ability of RXR-PPARgamma heterodimers to respond to ligands specific for either subunit. In contrast, the ability of RXR- and PPARgamma-specific ligands to synergize does not require the hormone-dependent activation domain of RXR. The results of in vitro and in vivo experiments indicate that binding of ligands to RXR alters the conformation of the dimerization partner, PPARgamma, and modulates the activity of the heterodimer in a manner independent of the RXR hormone-dependent activation domain.

MeSH Terms
3T3 Cells Adipocytes/cytology Animals Binding Sites Cell Differentiation DNA-Binding Proteins/metabolism Dimerization Histone Acetyltransferases Ligands Macromolecular Substances Mice Microbodies/metabolism Nuclear Proteins/metabolism Nuclear Receptor Coactivator 1 Protein Conformation Receptors, Cytoplasmic and Nuclear/metabolism Receptors, Retinoic Acid/metabolism Retinoid X Receptors Transcription Factors/metabolism Transcriptional Activation
Chemicals
DNA-Binding Proteins Ligands Macromolecular Substances Nuclear Proteins Receptors, Cytoplasmic and Nuclear Receptors, Retinoic Acid Retinoid X Receptors Transcription Factors Histone Acetyltransferases Ncoa1 protein, mouse Nuclear Receptor Coactivator 1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Schulman I G
Department of Retinoid Research, Ligand Pharmaceuticals, San Diego, California 92121, USA. ischulman@ligand.com
Shao G
Heyman R A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.6.3483
Email
ischulman@ligand.com
Published
1998-06-00
Pages
3483-94
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC108929
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.18.6.3483 PMC Full Text View journal details
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