Estrogen Receptor Pathways to AP-1

J Steroid Biochem Mol Biol. 2000 Nov 30;74(5):311-7. doi: 10.1016/s0960-0760(00)00108-4.

Abstract

Estrogen receptor (ER) binds to estrogen response elements in target genes and recruits a coactivator complex of CBP-pl60 that mediates stimulation of transcription. ER also activates transcription at AP-1 sites that bind the Jun/Fos transcription factors, but not ER. We review the evidence regarding mechanisms whereby ER increases the activity of Jun/Fos and propose two pathways of ER action depending on the ER (alpha or beta) and on the ligand. We propose that estrogen-ERalpha complexes use their activation functions (AF-1 and AF-2) to bind to the p 160 component of the coactivator complex recruited by Jun/Fos and trigger the coactivator to a higher state of activity. We propose that selective estrogen receptor modulator (SERM) complexes with ERbeta and with truncated ERalpha derivatives use their DNA binding domain to titrate histone deacetylase (HDAC)-repressor complexes away from the Jun/Fos coactivator complex, thereby allowing unfettered activity of the coactivators. Finally, we consider the possible physiological significance of ER action at AP-1 sites.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Gene Expression Regulation* / drug effects
  • Humans
  • Models, Genetic
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / metabolism*
  • Repressor Proteins / metabolism
  • Response Elements / genetics
  • Selective Estrogen Receptor Modulators / metabolism
  • Selective Estrogen Receptor Modulators / pharmacology
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / metabolism*

Substances

  • Receptors, Estrogen
  • Repressor Proteins
  • Selective Estrogen Receptor Modulators
  • Transcription Factor AP-1