title: The von hippel-lindau protein suppresses androgen receptor activity.
abstract: The androgen receptor (AR) plays a pivotal role in prostate homeostasis and prostate cancer development. To understand the mechanism underlying the regulation of the AR holds a promise for developing novel therapeutic approaches for prostate cancer. Here, we show that the Von Hippel-Lindau gene product, pVHL, physically interacts with AR and inhibits AR transcription activity but does not induce AR turnover. Moreover, pVHL also suppresses androgen-induced cell proliferation, implicating a physiological role of pVHL in androgen-induced signaling pathway. In addition, we provide evidence to show that pVHL actually enhanced AR de-ubiquitination instead of inducing AR ubiquitination, uncovering a noncanonical role of pVHL in the ubiquitin proteasome pathway. Our data reveal a novel function of pVHL in the regulation of AR transcription activity, which may expand the scope of pVHL in tumor suppression and provide mechanistic insight into prostate cancer initiation and progression.
authors.affiliation: The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Ouyang
authors.forename: Wuhan
authors.initials: W
authors.lastname: Xiao
mesh_terms: D000727:Androgen-Binding Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D051381:Rats; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D054875:Ubiquitination; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000737:chemistry / Q000502:physiology*
chemical_list: D000727:Androgen-Binding Protein; D004268:DNA-Binding Proteins; C119753:RNF6 protein, human; D011944:Receptors, Androgen; C027519:probasin; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C549870:KLK3 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; D017430:Prostate-Specific Antigen; C497446:VHL protein, human