Trihydrophobin 1 attenuates androgen signal transduction through promoting androgen receptor degradation.
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.
Yang
Yanzhong
Y
Gene Research Center, Key Laboratory of Glycoconjugate Research Ministry of Public Health, Shanghai Medical College of Fudan University, Shanghai 200032, PR China.
Zou
Weiying
W
Kong
Xiangfei
X
Wang
Hanzhou
H
Zong
Hongliang
H
Jiang
Jianhai
J
Wang
Yanlin
Y
Hong
Yi
Y
Chi
Yayun
Y
Xie
Jianhui
J
Gu
Jianxin
J
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000235:genetics; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics; D054875:Ubiquitination
D000728:Androgens; D002352:Carrier Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; C550274:TH1L protein, mouse; D014157:Transcription Factors; C118437:negative elongation factor; D017430:Prostate-Specific Antigen