Estrogen receptor, a common interaction partner for a subset of nuclear receptors

Mol Endocrinol. 1998 Aug;12(8):1184-92. doi: 10.1210/mend.12.8.0146.


Nuclear receptors regulate transcription by binding to specific DNA response elements as homodimers or heterodimers. Herein, the yeast and mammalian two-hybrid tests as well as glutathione-S-transferase pull-down assays were exploited to demonstrate that estrogen receptor (ER) directly binds to a subset of nuclear receptors through protein-protein interactions between ligand-binding domains. These receptors include hepatocyte nuclear factor 4, thyroid hormone receptor (TR), retinoic acid receptor (RAR), ERbeta, and retinoid X receptor (RXR). In yeast cells, a LexA fusion protein to the human ER ligand-binding domain (LexA/ER-LBD) was an inert transactivator of a LacZ reporter gene controlled by upstream LexA-binding sites. However, LexA/ER-LBD differentially modulated the LacZ reporter gene expression when coexpressed with native TRs, RARs, or RXRs. Similarly, cotransfection of these receptors in CV1 cells up- or down-regulated transactivations by ER. From these results, we propose that ER is a common interaction partner for a subset of receptors, and these interactions should mediate novel signaling pathways in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Binding Sites
  • DNA-Binding Proteins*
  • Hepatocyte Nuclear Factor 4
  • Humans
  • Phosphoproteins / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Retinoid X Receptors
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Transcription Factors / metabolism
  • Yeasts / genetics
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism


  • Bacterial Proteins
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 4
  • LexA protein, Bacteria
  • MLX protein, human
  • Phosphoproteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Recombinant Proteins
  • Retinoid X Receptors
  • Transcription Factors
  • beta-Galactosidase
  • Serine Endopeptidases