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

被引:154
作者
Reutens, AT
Fu, MF
Wang, CG
Albanese, C
McPhaul, MJ
Sun, ZJ
Balk, SP
Jänne, OA
Palvimo, JJ
Pestell, RG
机构
[1] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA
[2] Stanford Univ, Sch Med, Dept Surg & Genet, Stanford, CA 94305 USA
[3] Beth Israel Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA
[4] Univ Helsinki, Inst Biomed, Dept Physiol, FIN-00014 Helsinki, Finland
[5] Univ Helsinki, Dept Clin Chem, FIN-00014 Helsinki, Finland
[6] Albert Einstein Coll Med, Albert Einstein Comprehens Canc Ctr, Dept Dev & Mol Biol, Div Hormone Dependent Tumor Biol, Bronx, NY 10461 USA
关键词
D O I
10.1210/me.15.5.797
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The androgen receptor (AR) is a ligand-regulated member of the nuclear receptor superfamily. The cyclin Of 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 Of 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.
引用
收藏
页码:797 / 811
页数:15
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