Activation of PPARgamma coactivator-1 through transcription factor docking

Science. 1999 Nov 12;286(5443):1368-71. doi: 10.1126/science.286.5443.1368.

Abstract

Transcriptional coactivators have been viewed as constitutively active components, using transcription factors mainly to localize their functions. Here, it is shown that PPARgamma coactivator-1 (PGC-1) promotes transcription through the assembly of a complex that includes the histone acetyltransferases steroid receptor coactivator-1 (SRC-1) and CREB binding protein (CBP)/p300. PGC-1 has a low inherent transcriptional activity when it is not bound to a transcription factor. The docking of PGC-1 to peroxisome proliferator-activated receptor gamma (PPARgamma) stimulates an apparent conformational change in PGC-1 that permits binding of SRC-1 and CBP/p300, resulting in a large increase in transcriptional activity. Thus, transcription factor docking switches on the activity of a coactivator protein.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • COS Cells
  • DNA-Binding Proteins / metabolism
  • E1A-Associated p300 Protein
  • Gene Expression Regulation
  • Histone Acetyltransferases
  • Mice
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Nuclear Receptor Coactivator 1
  • Nuclear Respiratory Factors
  • Protein Binding
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transfection

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Nuclear Respiratory Factors
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • peroxisome-proliferator-activated receptor-gamma coactivator-1
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse
  • Histone Acetyltransferases
  • Ncoa1 protein, mouse
  • Nuclear Receptor Coactivator 1