Loss and/or inactivation of the VHL (von Hippel–Lindau) tumour suppressor causes various tumours. Using a yeast two-hybrid system, we have identified the AR (androgen receptor) co-activator UXT (ubiquitously expressed transcript), as a VHL-interacting protein. GST pull-down and co-immunoprecipitation assays show that UXT interacts with VHL. In addition, UXT recruits VHL to the nucleus. VHL associates with the DBD (DNA-binding domain) and hinge domains of the AR and induces AR ubiquitination. Moreover, VHL interaction with the AR activates AR transactivation upon DHT (dihydrotestosterone) treatment. VHL knockdown inhibits AR ubiquitination and decreases transcriptional activation of the AR. Our data suggest that the VHL–UXT interaction and VHL-induced ubiquitination of AR regulate transcriptional activation of the AR.
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Research Article|
October 24 2013
Regulation of the transcriptional activation of the androgen receptor by the UXT-binding protein VHL
Shuliang Chen;
Shuliang Chen
*Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China
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Ke Chen;
Ke Chen
*Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China
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Qinghua Zhang;
Qinghua Zhang
*Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China
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Hanhua Cheng;
Hanhua Cheng
1
*Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China
1Correspondence may be addressed to either of these authors (email hhcheng@whu.edu.cn or rjzhou@whu.edu.cn).
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Rongjia Zhou
Rongjia Zhou
1
*Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China
1Correspondence may be addressed to either of these authors (email hhcheng@whu.edu.cn or rjzhou@whu.edu.cn).
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Publisher: Portland Press Ltd
Received:
November 12 2012
Revision Received:
August 19 2013
Accepted:
August 21 2013
Accepted Manuscript online:
August 21 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 456 (1): 55–66.
Article history
Received:
November 12 2012
Revision Received:
August 19 2013
Accepted:
August 21 2013
Accepted Manuscript online:
August 21 2013
Citation
Shuliang Chen, Ke Chen, Qinghua Zhang, Hanhua Cheng, Rongjia Zhou; Regulation of the transcriptional activation of the androgen receptor by the UXT-binding protein VHL. Biochem J 15 November 2013; 456 (1): 55–66. doi: https://doi.org/10.1042/BJ20121711
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