SENP1 enhances androgen receptor-dependent transcription through desumoylation of histone deacetylase 1

被引:155
作者
Cheng, JK
Wang, DC
Wang, ZX
Yeh, ETH
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Cardiol, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
[3] Univ Texas, Hlth Sci Ctr, Res Ctr Cardiovasc Dis, Inst Mol Med Prevent Human Dis, Houston, TX 77030 USA
关键词
D O I
10.1128/MCB.24.13.6021-6028.2004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
SUMO (also called Sentrin) is a ubiquitin-like protein that plays an important role in regulating protein function and localization. It is known that several nuclear receptors are modified by SUMO; however, the effect of desumoylation in regulating nuclear receptor function has not been elucidated. Here we show that androgen receptor (AR)-mediated transcription is markedly enhanced by SENP1, a member of SUMO-specific protease family. SENP1's ability to enhance AR-dependent transcription is not mediated through desumoylation of AR, but rather through its ability to deconjugate histone deacetylase 1 (HDAC1), thereby reducing its deacetylase activity. HDAC1's repressive effect on AR-dependent transcription could be reversed by SENP1 and by deletion of its sumoylation sites. RNA interference depletion of endogenous HDAC1 also reduced SENP1's effect. Thus, SENP1 could regulate AR-dependent transcription through desumoylation of HDAC1. These studies provide insights on the potential role of desumoylation in the regulation of nuclear receptor activity.
引用
收藏
页码:6021 / 6028
页数:8
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