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Trihydrophobin 1 attenuates androgen signal transduction through promoting androgen receptor degradation
Author(s) -
Yang Yanzhong,
Zou Weiying,
Kong Xiangfei,
Wang Hanzhou,
Zong Hongliang,
Jiang Jianhai,
Wang Yanlin,
Hong Yi,
Chi Yayun,
Xie Jianhui,
Gu Jianxin
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22484
Subject(s) - lncap , androgen receptor , androgen , prostate cancer , signal transduction , regulator , endocrinology , chemistry , medicine , cancer research , biology , microbiology and biotechnology , cancer , hormone , biochemistry , gene
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.