Repressive domain of unliganded human estrogen receptor alpha associates with Hsc70

Genes Cells. 2005 Dec;10(12):1095-102. doi: 10.1111/j.1365-2443.2005.00904.x.


Estrogen receptor (ER) is a hormone-inducible transcription factor as a member of the nuclear receptor gene superfamily. Unliganded ER is transcriptionally silent and capable of DNA binding; however, it is unable to suppress the basal activity of the target gene promoters, unlike non-steroid hormone receptors that associate with corepressors in the absence of their cognate ligands. To study the molecular basis of how unliganded human ERalpha is maintained silent in gene regulation upon the target gene promoters, we biochemically searched interactants for hERalpha, and identified heat shock protein 70 (Hsc70). Hsc70 appeared to associate with the N-terminal hormone binding E domain, that also turned out a transcriptionally repressive domain. Competitive association of Hsc70 with a best known coactivator p300 was observed. Thus, these findings suggest that Hsc70 associates with unliganded hERalpha, and thereby deters hERalpha from recruiting transcriptional coregulators, presumably as a component of chaperone complexes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Cells, Cultured
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Ligands*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Binding / genetics
  • Protein Interaction Mapping
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation / genetics
  • Transfection


  • Estrogen Receptor alpha
  • HSP70 Heat-Shock Proteins
  • Ligands
  • Molecular Chaperones
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins