Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)-dependent manner

Mol Endocrinol. 2001 May;15(5):797-811. doi: 10.1210/mend.15.5.0641.


The androgen receptor (AR) is a ligand-regulated member of the nuclear receptor superfamily. The cyclin D1 gene product, which encodes the regulatory subunit of holoenzymes that phosphorylate the retinoblastoma protein (pRB), promotes cellular proliferation and inhibits cellular differentiation in several different cell types. Herein the cyclin D1 gene product inhibited ligand-induced AR- enhancer function through a pRB-independent mechanism requiring the cyclin D1 carboxyl terminus. The histone acetyltransferase activity of P/CAF (p300/CBP associated factor) rescued cyclin D1-mediated AR trans-repression. Cyclin D1 and the AR both bound to similar domains of P/CAF, and cyclin D1 displaced binding of the AR to P/CAF in vitro. These studies suggest cyclin D1 binding to the AR may repress ligand-dependent AR activity by directly competing for P/CAF binding.

Publication types

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

MeSH terms

  • Acetyltransferases / antagonists & inhibitors
  • Acetyltransferases / metabolism
  • Acetyltransferases / physiology*
  • Amino Acid Sequence
  • Androgen Receptor Antagonists*
  • Blotting, Western
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Cyclin D1 / metabolism
  • Cyclin D1 / physiology*
  • Histone Acetyltransferases
  • Humans
  • Ligands
  • Male
  • Molecular Sequence Data
  • Mutation
  • Prostatic Neoplasms / metabolism
  • Receptors, Androgen / metabolism
  • Receptors, Androgen / physiology
  • Sequence Alignment
  • Signal Transduction / physiology*
  • Transcription Factors
  • Tumor Cells, Cultured
  • p300-CBP Transcription Factors


  • Androgen Receptor Antagonists
  • Cell Cycle Proteins
  • Ligands
  • Receptors, Androgen
  • Transcription Factors
  • Cyclin D1
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor