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Proteasome-associated Deubiquitinase Ubiquitin-Specific Protease 14 Regulates Prostate Cancer Proliferation by Deubiquitinating and Stabilizing Androgen Receptor

Proteasome-associated Deubiquitinase Ubiquitin-Specific Protease 14 Regulates Prostate Cancer Proliferation by Deubiquitinating and Stabilizing Androgen Receptor

Yuning Liao, Ningning Liu, Xianliang Hua, Jianyu Cai, Xiaohong Xia, Xuejun Wang, Hongbiao Huang, Jinbao Liu

Cell Death Dis. 2017 Feb 2;8(2):e2585.

PMID: 28151478

Abstract:

Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete. Increasing evidence suggests that deubiquitinases are involved in the regulation of cancer development and progression but the specific underlying mechanism often is not elucidated. In the current study, we have identified ubiquitin-specific protease 14 (USP14) as a novel regulator of AR, inhibiting the degradation of AR via deubiquitinating this oncoprotein in the androgen-responsive prostate cancer cells. We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells. Hence, we conclude that USP14 promotes prostate cancer progression likely through stabilization of AR, suggesting that USP14 could be a promising therapeutic target for prostate cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415062	Ubiquitin-Specific Protease 14 human			Price

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