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

J Biol Chem. 2002 Apr 19;277(16):13918-25. doi: 10.1074/jbc.M201134200. Epub 2002 Feb 19.


Peroxisome proliferator-activated receptor gamma 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) alpha, 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 ERalpha in an estrogen-dependent manner. PERC and PGC-1 are likely to have different functions in ER signaling. Whereas PERC acts selectively on ERalpha and not on the second estrogen receptor ERbeta, PGC-1 coactivates strongly both ERs. Moreover, PERC and PGC-1 show distinct preferences for enhancing ERalpha in different promoter contexts. Finally, PERC enhances the ERalpha-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • Estrogen Receptor alpha
  • HeLa Cells
  • Humans
  • Ligands
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism
  • Myocardium / metabolism
  • Plasmids / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins
  • Receptors, Estrogen / metabolism*
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques


  • Carrier Proteins
  • Estrogen Receptor alpha
  • Ligands
  • PPARGC1B protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Estrogen
  • Transcription Factors
  • peroxisome-proliferator-activated receptor-gamma coactivator-1
  • RNA

Associated data

  • GENBANK/AF468496
  • GENBANK/AF468497