Regulation of the transcriptional activation of the androgen receptor by the UXT binding protein VHL

Loss and/or inactivation of VHL (the von Hippel Lindau tumour suppressor) cause various tumours. Using a yeast two-hybrid system, we have identified an AR co-activator, UXT, 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 and hinge domains of the AR and induces AR ubiquitination. Moreover, VHL interaction with the AR activates AR transactivation upon DHT 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.

Source: BJ Gene - August 21, 2013 Category: Biochemistry Authors: S Chen, K Chen, Q Zhang, H Cheng, R Zhou Tags: BJ Signal Source Type: research