Destruction of Full-Length Androgen Receptor by Wild-Type SPOP, but Not Prostate-Cancer-Associated Mutants

Jian An, Chenji Wang, Yibin Deng, Long Yu, Haojie Huang

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

The SPOP E3 ubiquitin ligase gene is frequently mutated in human prostate cancers. Here, we demonstrate that SPOP recognizes a Ser/Thr-rich degron in the hinge domain of androgen receptor (AR) and induces degradation of full-length AR and inhibition of AR-mediated gene transcription and prostate cancer cell growth. AR splicing variants, most ofwhich lack the hinge domain, escape SPOP-mediated degradation. Prostate-cancer-associated mutants of SPOP cannot bind to and promote ARdestruction. Furthermore, androgens antagonize SPOP-mediated degradation of AR, whereas antiandrogens promote this process. This study identifies AR as a bona fide substrate of SPOP and elucidates a role of SPOP mutations in prostate cancer, thus implying the importance of this pathway in resistance to antiandrogen therapy of prostate cancer.

Original languageEnglish (US)
Pages (from-to)657-669
Number of pages13
JournalCell Reports
Volume6
Issue number4
DOIs
StatePublished - 2014

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Androgen Receptors
Prostatic Neoplasms
Androgen Antagonists
Hinges
Degradation
Genes
Ubiquitin-Protein Ligases
Cell growth
Transcription
Androgens
Mutation
Substrates
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Destruction of Full-Length Androgen Receptor by Wild-Type SPOP, but Not Prostate-Cancer-Associated Mutants. / An, Jian; Wang, Chenji; Deng, Yibin; Yu, Long; Huang, Haojie.

In: Cell Reports, Vol. 6, No. 4, 2014, p. 657-669.

Research output: Contribution to journalArticle

An, Jian ; Wang, Chenji ; Deng, Yibin ; Yu, Long ; Huang, Haojie. / Destruction of Full-Length Androgen Receptor by Wild-Type SPOP, but Not Prostate-Cancer-Associated Mutants. In: Cell Reports. 2014 ; Vol. 6, No. 4. pp. 657-669.
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