Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)-dependent manner.
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.
Reutens
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AT
The Albert Einstein Comprehensive Cancer Center, Division of Hormone-Dependent Tumor Biology, Department of Developmental and Molecular Biology Albert Einstein College of Medicine Bronx, New York 10461, USA.
Fu
M
M
Wang
C
C
Albanese
C
C
McPhaul
M J
MJ
Sun
Z
Z
Balk
S P
SP
Jänne
O A
OA
Palvimo
J J
JJ
Pestell
R G
RG
D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D059002:Androgen Receptor Antagonists; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism / Q000502:physiology*; D051548:Histone Acetyltransferases; D006801:Humans; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011471:Prostatic Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D059002:Androgen Receptor Antagonists; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D051548:Histone Acetyltransferases; D008024:Ligands; D011944:Receptors, Androgen; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor