Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)-dependent manner
Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)-dependent manner
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DOI：
10.1210/me.15.5.797
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发表时间：
2001-05-01
影响因子：
--
通讯作者：
Pestell, RG
中科院分区：
文献类型：
--
作者：
Reutens, AT;Fu, MF;Pestell, RG
雄激素受体（AR）是核受体超家族中配体调控的成员。细胞周期蛋白Of基因产物编码使视网膜母细胞瘤蛋白（pRB）磷酸化的全酶调控亚基，在几种不同的细胞类型中促进细胞增殖并抑制细胞分化。在这里，cyclin Of基因产物通过一种不依赖于prb的机制抑制配体诱导的ar增强子功能，这种机制需要cyclin D1羧基端。P/CAF （p300/CBP相关因子）的组蛋白乙酰转移酶活性挽救了细胞周期蛋白d1介导的AR反式抑制。Cyclin D1和AR都结合到P/CAF的相似结构域，并且Cyclin D1在体外取代了AR与P/CAF的结合。这些研究表明，cyclin D1与AR结合可能通过直接竞争P/CAF结合来抑制配体依赖性AR活性。
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.