Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma

Biochem Biophys Res Commun. 2003 Dec 26;312(4):975-82. doi: 10.1016/j.bbrc.2003.11.025.

Abstract

Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor highly expressed in heart, skeletal muscle, kidney, and brain. To identify activation function-1 (AF-1)-dependent cofactors involved in the transcriptional function of ERRgamma, we screened for human cDNAs coding for proteins that bind to the bacterial expressed AF-1 by biopanning of a phage display library. Phages displaying fusion proteins with full-length PNRC2 (proline-rich nuclear receptor co-regulatory protein 2), already shown to be a cofactor for other nuclear receptors, and with a polypeptide of the bHLH corepressor TLE1 bound to the AF-1 containing bait. Pull-down analyses demonstrated a direct interaction of the receptor with the newly identified full-length proteins. Surprisingly, not only PNRC2 but also the corepressor TLE1 functioned as ERRgamma coactivator in a reporter gene analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Brain / metabolism*
  • Brain Chemistry
  • Cells, Cultured
  • Chlorocebus aethiops
  • Co-Repressor Proteins
  • Humans
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Receptors, Interferon / chemistry
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins*
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / physiology*
  • Transcriptional Activation

Substances

  • Co-Repressor Proteins
  • ESRRG protein, human
  • IFNGR2 protein, human
  • Ifngr2 protein, mouse
  • Nuclear Proteins
  • PNRC2 protein, human
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • Receptors, Interferon
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • TLE1 protein, human
  • Trans-Activators
  • Transcription Factors