Estrogen receptor activation function 1 works by binding p160 coactivator proteins

Mol Endocrinol. 1998 Oct;12(10):1605-18. doi: 10.1210/mend.12.10.0185.

Abstract

Estrogen receptor-alpha contains two transactivation functions, a weak constitutive activation function (AF-1) and a hormone-dependent activation function (AF-2). AF-2 works by recruiting a large coactivator complex, composed of one or more p160s, CREB-binding protein (CBP)/p300, and P/CAF (p300 and CBP-associated factor), via direct contacts with the p160s. We report here that independent AF-1 activity also requires p160 contacts. Unlike AF-2, which binds signature NR boxes in the center of the p160 molecule, AF-1 binds to sequences near the p160 C terminus. We propose that the ability of AF-1 and AF-2 to interact with separate surfaces of the same coactivator is important for the ability of these transactivation functions to synergize.

Publication types

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

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Binding Sites
  • CREB-Binding Protein
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • HeLa Cells / drug effects
  • HeLa Cells / metabolism
  • Histone Acetyltransferases
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 2
  • Nuclear Receptor Coactivator 3
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Tamoxifen / pharmacology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • p300-CBP Transcription Factors

Substances

  • Cell Cycle Proteins
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • NCOA2 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Coactivator 2
  • Peptide Fragments
  • Receptors, Estrogen
  • Recombinant Proteins
  • Trans-Activators
  • Transcription Factors
  • Tamoxifen
  • Acetyltransferases
  • CREB-Binding Protein
  • CREBBP protein, human
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • NCOA3 protein, human
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 3
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor