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

  1. Author:
    Xu, K. X.
    Shimelis, H.
    Linn, D. E.
    Jiang, R. C.
    Yang, X.
    Sun, F.
    Guo, Z. Y.
    Chen, H. G.
    Li, W.
    Chen, H. G.
    Kong, X. T.
    Melamed, J.
    Fang, S. Y.
    Xiao, Z.
    Veenstra, T. D.
    Qiu, Y.

  2. Author Address

    Xu, Kexin, Shimelis, Hermela, Linn, Douglas E.; Jiang, Richeng, Yang, Xi, Sun, Feng, Guo, Zhiyong, Chen, Hege, Li, Wei, Qiu, Yun] Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. [Xu, Kexin, Shimelis, Hermela, Linn, Douglas E.; Jiang, Richeng, Yang, Xi, Sun, Feng, Guo, Zhiyong, Chen, Hege, Li, Wei, Qiu, Yun] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Chen, Hegang] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Kong, Xiangtian, Melamed, Jonathan] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Fang, Shengyun] Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Baltimore, MD 21201 USA. [Xiao, Zhen, Veenstra, Timothy D.] SAIC Frederick Inc, NCI, Lab Prote & Analyt Technol, Frederick, MD 21702 USA.
    1. Year: 2009
  2. Journal: Cancer Cell
    1. 15
    2. 4
    3. Pages: 270-282
  4. Type of Article: Article
  1. 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.

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External Sources

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  2. DOI: 10.1016/j.ccr.2009.02.021
  3. PMID: 19345326

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