Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor.

Cheng S; Brzostek S; Lee SRHollenberg ANBalk SP

首页> 外文期刊>Molecular Endocrinology >Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor.

【24h】

Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor.

机译：Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor.

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Nuclear receptor corepressor (NCoR) mediates transcriptional repression by unliganded nuclear receptors and certain steroid hormone receptors (SHRs) bound to nonphysiological antagonists, but has not been found to regulate SHRs bound to their natural ligands. This report demonstrates that NCoR interacts directly with the androgen receptor (AR) and represses dihydrotestosterone-stimulated AR transcriptional activity. The NCoR C terminus, containing the receptor interacting domains, was necessary for repression, which was ablated by mutations in the corepressor nuclear receptor (CoRNR) boxes. In contrast, the NCoR N terminus, containing domains that can recruit histone deacetylases, was not necessary for repression. Binding studies in vitro with a series of glutathione-S-transferase-NCoR and -AR fusion proteins demonstrated a direct interaction that was similarly dependent upon the NCoR corepressor nuclear receptor boxes and AR ligand binding domain and was independent of ligand and helix 12 in the AR ligand binding domain. This NCoR-AR interaction was further demonstrated in mammalian two-hybrid assays and by coimmunoprecipitation of the endogenous proteins from a prostate cancer cell line. Finally, AR transcriptional activity could be enhanced in vivo by sequestration of endogenous NCoR with unliganded thyroid hormone receptor. These results demonstrate that AR, in contrast to other SHRs, is regulated by NCoR and suggest the possibility of developing selective AR modulators that enhance this interaction.

著录项

来源
《Molecular Endocrinology》 |2002年第7期|1492-1501|共10页
作者
Cheng S; Brzostek S; Lee SRHollenberg ANBalk SP;
展开▼
作者单位

Cancer Biology Program, Division of Hematology-Oncology (S.C., S.R.L., S.P.B.) and Thyroid Unit, Division of Endocrinology (S.B., A.N.H.), Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 022;

bh.med.kyoto-u.ac.jp;

展开▼
收录信息
原文格式 PDF
正文语种英语
中图分类内分泌腺疾病及代谢病;内分泌生理学;
关键词
receptor; binding; Receptors; Nuclear;

Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor.

摘要

著录项

相关主题

期刊订阅