Agonist-antagonist induced coactivator and corepressor interplay on the human androgen receptor

Mol Cell Endocrinol. 2003 Dec 31;213(1):79-85. doi: 10.1016/j.mce.2003.10.036.


The human androgen receptor (AR) is a member of the nuclear hormone receptor superfamily. However, in contrast to other members of this family the amino-(N)-terminus of AR harbors the major transactivation function. Previously we have shown that hormone antagonists that bind to the carboxy-terminal ligand-binding domain repress AR through recruitment of corepressors that are recruited to the receptor N-terminus. Here we show by a modified mammalian two-hybrid system that both the AR interacting domains of the coactivator SRC1 and of the corepressor SMRT compete for interaction with the AR N-terminus. In contrast to other members of the nuclear receptor superfamily the LXXLL motifs of SRC1e are not required for this interaction, instead a stretch of 135 amino acids of the glutamine rich region (Qr) of SRC1e is essential to bind to the AR N-terminus. We show that the Qr-region of SRC1 is able to inhibit the interaction of SMRT with AR. Also, we demonstrate that the corepressor mediated repression decreases the antagonist-induced transactivation while, surprisingly, it increases the agonist-induced transactivation. This may indicate that coactivators and corepressors act in concert to dictate the overall receptor-mediated action dependent on the type of ligand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Receptor Antagonists
  • Androgens
  • Binding, Competitive
  • Cyproterone Acetate / pharmacology
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology
  • Histone Acetyltransferases
  • Humans
  • Ligands
  • Nuclear Receptor Co-Repressor 2
  • Nuclear Receptor Coactivator 1
  • Protein Binding / drug effects
  • Protein Interaction Mapping
  • Receptors, Androgen / metabolism*
  • Repressor Proteins / metabolism*
  • Repressor Proteins / physiology
  • Trans-Activators / metabolism*
  • Trans-Activators / physiology
  • Transcription Factors / metabolism
  • Transcription Factors / physiology


  • Androgen Receptor Antagonists
  • Androgens
  • DNA-Binding Proteins
  • Ligands
  • NCOR2 protein, human
  • Nuclear Receptor Co-Repressor 2
  • Receptors, Androgen
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Cyproterone Acetate
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1