The E3 Ubiquitin Ligase Siah2 Contributes to Castration-Resistant Prostate Cancer by Regulation of Androgen Receptor Transcriptional Activity

ArticleinCancer cell 23(3):332-46 · March 2013with42 Reads
Impact Factor: 23.52 · DOI: 10.1016/j.ccr.2013.02.016 · Source: PubMed
Abstract

Understanding the mechanism underlying the regulation of the androgen receptor (AR), a central player in the development of castration-resistant prostate cancer (CRPC), holds promise for overcoming the challenge of treating CRPC. We demonstrate that the ubiquitin ligase Siah2 targets a select pool of NCOR1-bound, transcriptionally-inactive AR for ubiquitin-dependent degradation, thereby promoting expression of select AR target genes implicated in lipid metabolism, cell motility, and proliferation. Siah2 is required for prostate cancer cell growth under androgen-deprivation conditions in vitro and in vivo, and Siah2 inhibition promotes prostate cancer regression upon castration. Notably, Siah2 expression is markedly increased in human CRPCs. Collectively, we find that selective regulation of AR transcriptional activity by the ubiquitin ligase Siah2 is important for CRPC development.

Full-text

Available from: William Placzek, Feb 10, 2014
Cancer Cell
Erratum
The E3 Ubiquitin Ligase Siah2 Contributes to
Castration-Resistant Prostate Cancer by Regulation
of Androgen Receptor Transcriptional Activity
Jianfei Qi,
*
Manisha Tripathi, Rajeev Mishra, Natasha Sahgal, Ladan Fazli, Susan Ettinger, William J. Placzek,
Giuseppina Claps, Leland W.K. Chung, David Bowtell, Martin Gleave, Neil Bhowmick, and Ze’ev A. Ronai
*
*Correspondence: jfqi@sbmri.org (J.Q.), ronai@sbmri.org (Z.A.R.)
http://dx.doi.org/10.1016/j.ccr.2013.05.018
(Cancer Cell 23, 332–346; March 18, 2013)
Dr. Laden Fazli’s name was spelled incorrectly as ‘Fazil’ in the original article. It appears correctly in this erratum.
Cancer Cell 23, 853, June 10, 2013 ª2013 Elsevier Inc. 853
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