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Trihydrophobin 1 attenuates androgen signal transduction through promoting androgen receptor degradation

✍ Scribed by Yanzhong Yang; Weiying Zou; Xiangfei Kong; Hanzhou Wang; Hongliang Zong; Jianhai Jiang; Yanlin Wang; Yi Hong; Yayun Chi; Jianhui Xie; Jianxin Gu

Book ID
102876105
Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
794 KB
Volume
109
Category
Article
ISSN
0730-2312

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✦ Synopsis

Abstract

The androgen‐signaling pathway plays critical roles in normal prostate development, benign prostatic hyperplasia, established prostate cancer, and in prostate carcinogenesis. In this study, we report that trihydrophobin 1 (TH1) is a potent negative regulator to attenuate the androgen signal‐transduction cascade through promoting androgen receptor (AR) degradation. TH1 interacts with AR both in vitro and in vivo, decreases the stability of AR, and promotes AR ubiquitination in a ligand‐independent manner. TH1 also associates with AR at the active androgen‐responsive prostate‐specific antigen (PSA) promoter in the nucleus of LNCaP cells. Decrease of endogenous AR protein by TH1 interferes with androgen‐induced luciferase reporter expression and reduces endogenous PSA expression. Taken together, these results indicate that TH1 is a novel regulator to control the duration and magnitude of androgen signal transduction and might be directly involved in androgen‐related developmental, physiological, and pathological processes. J. Cell. Biochem. 109: 1013–1024, 2010. © 2010 Wiley‐Liss, Inc.

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## Abstract The androgen receptor (AR) is a ligand‐dependent transcription factor belonging to the steroid hormone receptor superfamily. Under normal conditions, in the absence of a ligand, the AR is localized to the cytoplasm and is actively transported into the nucleus upon binding of androgens.