IR@PKUHSC  > 北京大学第一临床医学院  > 泌尿外科
学科主题临床医学
Nuclear Export Signal of Androgen Receptor (NESAR) Regulation of Androgen Receptor Level in Human Prostate Cell Lines via Ubiquitination and Proteasome-Dependent Degradation
Gong, Yanqing1,2,4; Wang, Dan4; Dar, Javid A.4; Singh, Prabhpreet4; Graham, Lara4; Liu, Weijun4; Ai, Junkui4; Xin, Zhongcheng1,2; Guo, Yinglu1,2; Wang, Zhou4,5
刊名ENDOCRINOLOGY
2012-12-01
DOI10.1210/en.2012-1841
153期:12页:5716-5725
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]AGGRESOME FORMATION ; LIVING CELLS ; CANCER CELLS ; BINDING ; SYNPHILIN-1 ; DYNAMICS ; PHOSPHORYLATION ; OVEREXPRESSION ; STABILIZATION ; TRANSCRIPTION
英文摘要

Androgen receptor (AR) plays a key role in prostate development and carcinogenesis. Increased expression and/or stability of AR is associated with sensitization of prostate cancer cells to low levels of androgens, leading to castration resistance. Hence, understanding the mechanisms regulating AR protein stability is clinically relevant and may lead to new approaches to prevent and/or treat prostate cancer. Using fluorescence microscopy, Western blot, and pulse chase assay, we showed that nuclear export signal (NES)(AR), a nuclear export signal in the ligand binding domain (LBD) of AR, can significantly enhance the degradation of fusion protein constructs in PC3 prostate cancer cells. The half-life of GFP-NESAR was less than 3 h, which was 10 times shorter than that of green fluorescent protein (GFP) control. Further analysis showed tha tNES(AR) can signal for polyubiquitination and that degradation of NESAR-containing fusion proteins can be blocked by proteasome inhibitor MG132. Ubiquitination of GFP-AR or GFP-LBD was suppressed in the presence of dihydrotestosterone, which is known to suppress NESAR while inducing nuclear localization signal 2 in AR or LBD, suggesting that the export activity of NESAR is required for NESAR-mediated polyubiquitination. Treatment with MG132 also induced aggresome formation of NESAR-containing fusion proteins in perinuclear regions of the transfected PC3 cells, indicating a role for NESAR in inducing unfolded protein responses. The above observations suggest that NESAR plays a key role in AR ubiquitination and proteasome-dependent degradation in prostate cancer cells. (Endocrinology 153: 5716-5725, 2012)

语种英语
WOS记录号WOS:000311752300005
项目编号R01 CA108675 ; R37 DK51193 ; P50 CA090386
资助机构National Institutes of Health ; China Scholarship Council
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60475
专题北京大学第一临床医学院_泌尿外科
北京大学第一临床医学院_北京大学泌尿外科研究所
作者单位1.Peking Univ, Inst Urol, Beijing 100034, Peoples R China
2.Natl Urol Canc Ctr, Beijing 100034, Peoples R China
3.Peking Univ, Dept Urol, Peking Univ Hosp 1, Beijing 100034, Peoples R China
4.Univ Pittsburgh, Sch Med, Dept Urol, Inst Canc, Pittsburgh, PA 15232 USA
5.Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Inst Canc, Pittsburgh, PA 15232 USA
推荐引用方式
GB/T 7714
Gong, Yanqing,Wang, Dan,Dar, Javid A.,et al. Nuclear Export Signal of Androgen Receptor (NESAR) Regulation of Androgen Receptor Level in Human Prostate Cell Lines via Ubiquitination and Proteasome-Dependent Degradation[J]. ENDOCRINOLOGY,2012,153(12):5716-5725.
APA Gong, Yanqing.,Wang, Dan.,Dar, Javid A..,Singh, Prabhpreet.,Graham, Lara.,...&Wang, Zhou.(2012).Nuclear Export Signal of Androgen Receptor (NESAR) Regulation of Androgen Receptor Level in Human Prostate Cell Lines via Ubiquitination and Proteasome-Dependent Degradation.ENDOCRINOLOGY,153(12),5716-5725.
MLA Gong, Yanqing,et al."Nuclear Export Signal of Androgen Receptor (NESAR) Regulation of Androgen Receptor Level in Human Prostate Cell Lines via Ubiquitination and Proteasome-Dependent Degradation".ENDOCRINOLOGY 153.12(2012):5716-5725.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Gong, Yanqing]的文章
[Wang, Dan]的文章
[Dar, Javid A.]的文章
百度学术
百度学术中相似的文章
[Gong, Yanqing]的文章
[Wang, Dan]的文章
[Dar, Javid A.]的文章
必应学术
必应学术中相似的文章
[Gong, Yanqing]的文章
[Wang, Dan]的文章
[Dar, Javid A.]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。