Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: a unique signaling pathway in the steroid receptor superfamily

Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14724-9. doi: 10.1073/pnas.96.26.14724.

Abstract

The androgen receptor (AR) binds to androgen response elements and regulates target genes via a mechanism involving coregulators. Here we demonstrate that the AR can interact with the testicular orphan receptor-4 (TR4) and function as a repressor to down-regulate the TR4 target genes by preventing the TR4 binding to its target DNA. Interestingly, the heterodimerization of AR and TR4 also allows TR4 to repress AR target gene expression. Simultaneous exposure to both receptors therefore could result in bidirectional suppression of their target genes. Together, these data demonstrate that the coupling of two different receptors, through the heterodimerization of AR and TR4, is a unique signaling pathway in the steroid receptor superfamily, which may facilitate further understanding of the complicated androgen action in prostate cancer or libido.

Publication types

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

MeSH terms

  • Dimerization
  • Gene Expression Regulation*
  • Humans
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Receptors, Thyroid Hormone*
  • Recombinant Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Response Elements
  • Signal Transduction
  • Transcriptional Activation
  • Two-Hybrid System Techniques

Substances

  • NR2C2 protein, human
  • Nerve Tissue Proteins
  • Receptors, Androgen
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • Recombinant Proteins
  • Repressor Proteins