The PGC-1-related protein PERC is a selective coactivator of estrogen receptor α

Dieter Kressler, Sylvia N. Schreiber, Darko Knutti, Anastasia Kralli

Research output: Contribution to journalArticle

Abstract

Peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) is a tissue-specific coactivator that enhances the activity of many nuclear receptors and coordinates transcriptional programs important for energy metabolism. We describe here a novel PGC-1-related coactivator that is expressed in a similar tissue-specific manner as PGC-1, with the highest levels in heart and skeletal muscle. In contrast to PGC-1, the new coactivator shows high receptor specificity. It enhances potently the activity of estrogen receptor (ER) α, while having only small effects on other receptors. Because of its nuclear receptor selectivity, we have termed the new protein PERC (PGC-1 related Estrogen Receptor Coactivator). We show here that the coactivation function of PERC relies on a bipartite transcriptional activation domain and two LXXLL motifs that interact with the AF2 domain of ERα in an estrogen-dependent manner. PERC and PGC-1 are likely to have different functions in ER signaling. Whereas PERC acts selectively on ERα and not on the second estrogen receptor ERβ, PGC-1 coactivates strongly both ERs. Moreover, PERC and PGC-1 show distinct preferences for enhancing ERα in different promoter contexts. Finally, PERC enhances the ERα-mediated response to the partial agonist tamoxifen, while PGC-1 modestly represses it. The two coactivators are likely to mediate distinct, tissue-specific responses to estrogens.

Original languageEnglish (US)
Pages (from-to)13918-13925
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number16
DOIs
StatePublished - Apr 19 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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