title: Regulation of the transcriptional activation of the androgen receptor by the UXT-binding protein VHL.
abstract: 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.
authors: *Department of Genetics, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors: Shuliang
authors: S
authors: Chen
authors: Ke
authors: K
authors: Chen
authors: Qinghua
authors: Q
authors: Zhang
authors: Hanhua
authors: H
authors: Cheng
authors: Rongjia
authors: R
authors: Zhou
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D054875:Ubiquitination; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; C118920:UXT protein, human; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; C494469:VHL protein, mouse