Modulation of estrogen receptor-α transcriptional activity by the coactivator PGC-1

Irina Tcherepanova, Pere Puigserver, John D. Norris, Bruce M. Spiegelman, Donald P. McDonnell

Research output: Contribution to journalArticlepeer-review

Abstract

A transcriptional coactivator of the peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ-coactivator-1(PGC-1) interacts in a constitutive manner with the hinge domain of PPARγ and enhances its transcriptional activity. In this study we demonstrate that PGC-1 is a coactivator of estrogen receptor-α (ERα)-dependent transcriptional activity. However the mechanism by which PGC-1 interacts with ERα is different from that of PPARγ. Specifically, it was determined that the carboxyl terminus of PGC-1 interacts in a ligand-independent manner with the ERα hinge domain. In addition, an LXXLL motif within the amino terminus of PGC-1 was shown to interact in an agonist-dependent manner with the AF2 domain within the carboxyl terminus of ERα. The ability of PGC-1 to associate with and potentiate the transcriptional activity of an ERα-AF2 mutant that is unable to interact with the p160 class of coactivators suggests that this coactivator may have a unique role in estrogen signaling. It is concluded from these studies that PGC-1 is a bona fide ERα coactivator, which may serve as a convergence point between PPARγ and ERα signaling.

Original languageEnglish (US)
Pages (from-to)16302-16308
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number21
DOIs
StatePublished - May 26 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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