A CBP Integrator Complex Mediates Transcriptional Activation and AP-1 Inhibition by Nuclear Receptors

Cell. 1996 May 3;85(3):403-14. doi: 10.1016/s0092-8674(00)81118-6.

Abstract

Nuclear receptors regulate gene expression by direct activation of target genes and inhibition of AP-1. Here we report that, unexpectedly, activation by nuclear receptors requires the actions of CREB-binding protein (CBP) and that inhibition of AP-1 activity is the apparent result of competition for limiting amounts of CBP/p300 in cells. Utilizing distinct domains, CBP directly interacts with the ligand-binding domain of multiple nuclear receptors and with the p160 nuclear receptor coactivators, which upon cloning have proven to be variants of the SRC-1 protein. Because CBP represents a common factor, required in addition to distinct coactivators for function of nuclear receptors, CREB, and AP-1, we suggest that CBP/p300 serves as an integrator of multiple signal transduction pathways within the nucleus.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Binding, Competitive / genetics
  • CREB-Binding Protein
  • Cloning, Molecular
  • Conserved Sequence
  • DNA, Complementary / genetics
  • Fibroblasts / physiology
  • Gene Expression Regulation / genetics
  • Histone Acetyltransferases
  • Ligands
  • Molecular Sequence Data
  • Molecular Weight
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / pharmacology*
  • Nuclear Receptor Coactivator 1
  • Rats
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Transcription Factor AP-1 / antagonists & inhibitors*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology*
  • Transcriptional Activation / drug effects*

Substances

  • DNA, Complementary
  • Ligands
  • Nuclear Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • Transcription Factor AP-1
  • Transcription Factors
  • CREB-Binding Protein
  • Crebbp protein, rat
  • Histone Acetyltransferases
  • Nuclear Receptor Coactivator 1