Regulation of Androgen Receptor Transcriptional Activity and Specificity by RNF6-Induced Ubiquitination

Kexin Xu; Hermela Shimelis; Douglas E. Linn; Richeng Jiang; Xi Yang; Feng Sun; Zhiyong Guo; Hege Chen; Wei Li; Hegang Chen; Xiangtian Kong; Jonathan Melamed; Shengyun Fang; Zhen Xiao; Timothy D. Veenstra; Yun Qiu

doi:10.1016/j.ccr.2009.02.021

Regulation of Androgen Receptor Transcriptional Activity and Specificity by RNF6-Induced Ubiquitination

Kexin Xu
, Hermela Shimelis
, Douglas E. Linn
, Richeng Jiang
, Xi Yang
, Feng Sun
, Zhiyong Guo
, Hege Chen
, Wei Li
, Hegang Chen
, Xiangtian Kong
, Jonathan Melamed
, Shengyun Fang
, Zhen Xiao
, Timothy D. Veenstra
, Yun Qiu

Research output: Contribution to journal › Article › peer-review

204 Scopus citations

Abstract

The androgen receptor (AR) plays a critical role in prostate cancer. We have identified a ubiquitin E3 ligase, RNF6, as an AR-associated protein in a proteomic screen. RNF6 induces AR ubiquitination and promotes AR transcriptional activity. Specific knockdown of RNF6 or mutation of RNF6-induced ubiquitination acceptor sites on AR selectively alters expression of a subset of AR target genes and diminishes recruitment of AR and its coactivators to androgen-responsive elements present in the regulatory region of these genes. Furthermore, RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Our data suggest that RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity through modulating cofactor recruitment.

Original language	English (US)
Pages (from-to)	270-282
Number of pages	13
Journal	Cancer Cell
Volume	15
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2009.02.021
State	Published - Apr 7 2009
Externally published	Yes

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccr.2009.02.021

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@article{5befc9c83d4c4b51becacd7062960847,

title = "Regulation of Androgen Receptor Transcriptional Activity and Specificity by RNF6-Induced Ubiquitination",

abstract = "The androgen receptor (AR) plays a critical role in prostate cancer. We have identified a ubiquitin E3 ligase, RNF6, as an AR-associated protein in a proteomic screen. RNF6 induces AR ubiquitination and promotes AR transcriptional activity. Specific knockdown of RNF6 or mutation of RNF6-induced ubiquitination acceptor sites on AR selectively alters expression of a subset of AR target genes and diminishes recruitment of AR and its coactivators to androgen-responsive elements present in the regulatory region of these genes. Furthermore, RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Our data suggest that RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity through modulating cofactor recruitment.",

keywords = "CELLCYCLE",

author = "Kexin Xu and Hermela Shimelis and Linn, \{Douglas E.\} and Richeng Jiang and Xi Yang and Feng Sun and Zhiyong Guo and Hege Chen and Wei Li and Hegang Chen and Xiangtian Kong and Jonathan Melamed and Shengyun Fang and Zhen Xiao and Veenstra, \{Timothy D.\} and Yun Qiu",

note = "Funding Information: We would like to thank B. Guan and C. Bieberich for their assistance with ubiquitination assays. This work was supported in part by NIH grant CA106504 and US Department of Defense (DOD) grants W81XWH-06-1-0199 and W81XWH-08-1-0126 to Y.Q., NIH grant NCI UO1-CA86772 to J.M., NIH contract NO1-CO-12400 to T.D.V., DOD Predoctoral Fellowship W81XWH-06-1-0005 to K.X., and DOD Predoctoral Fellowship W81XWH-08-1-0068 to D.E.L. ",

year = "2009",

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day = "7",

doi = "10.1016/j.ccr.2009.02.021",

language = "English (US)",

volume = "15",

pages = "270--282",

journal = "Cancer Cell",

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T1 - Regulation of Androgen Receptor Transcriptional Activity and Specificity by RNF6-Induced Ubiquitination

AU - Xu, Kexin

AU - Shimelis, Hermela

AU - Linn, Douglas E.

AU - Jiang, Richeng

AU - Yang, Xi

AU - Sun, Feng

AU - Guo, Zhiyong

AU - Chen, Hege

AU - Li, Wei

AU - Chen, Hegang

AU - Kong, Xiangtian

AU - Melamed, Jonathan

AU - Fang, Shengyun

AU - Xiao, Zhen

AU - Veenstra, Timothy D.

AU - Qiu, Yun

N1 - Funding Information: We would like to thank B. Guan and C. Bieberich for their assistance with ubiquitination assays. This work was supported in part by NIH grant CA106504 and US Department of Defense (DOD) grants W81XWH-06-1-0199 and W81XWH-08-1-0126 to Y.Q., NIH grant NCI UO1-CA86772 to J.M., NIH contract NO1-CO-12400 to T.D.V., DOD Predoctoral Fellowship W81XWH-06-1-0005 to K.X., and DOD Predoctoral Fellowship W81XWH-08-1-0068 to D.E.L.

PY - 2009/4/7

Y1 - 2009/4/7

N2 - The androgen receptor (AR) plays a critical role in prostate cancer. We have identified a ubiquitin E3 ligase, RNF6, as an AR-associated protein in a proteomic screen. RNF6 induces AR ubiquitination and promotes AR transcriptional activity. Specific knockdown of RNF6 or mutation of RNF6-induced ubiquitination acceptor sites on AR selectively alters expression of a subset of AR target genes and diminishes recruitment of AR and its coactivators to androgen-responsive elements present in the regulatory region of these genes. Furthermore, RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Our data suggest that RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity through modulating cofactor recruitment.

AB - The androgen receptor (AR) plays a critical role in prostate cancer. We have identified a ubiquitin E3 ligase, RNF6, as an AR-associated protein in a proteomic screen. RNF6 induces AR ubiquitination and promotes AR transcriptional activity. Specific knockdown of RNF6 or mutation of RNF6-induced ubiquitination acceptor sites on AR selectively alters expression of a subset of AR target genes and diminishes recruitment of AR and its coactivators to androgen-responsive elements present in the regulatory region of these genes. Furthermore, RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Our data suggest that RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity through modulating cofactor recruitment.

KW - CELLCYCLE

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AN - SCOPUS:63249104202

SN - 1535-6108

VL - 15

SP - 270

EP - 282

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

Regulation of Androgen Receptor Transcriptional Activity and Specificity by RNF6-Induced Ubiquitination

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