TRAF4 and Castration Resistant Prostate Cancer
Technical Report,08 Sep 2015,07 Sep 2016
Baylor College of Medicine Houston United States
Pagination or Media Count:
It is now well-recognized that AR remains to be a critical player in castration-resistant prostate cancers. It was suggested that the function of AR in CRPC is not to turn on the same transcriptional targeted genes in the absence of androgen but to turn on a distinct set of genes independent of androgen. However, it was not clear what triggers the functional switch of AR. Here we report another pathway to bypass androgen dependency through AR ubiquitination. We found that TRAF4, a RING domain E3 ubiquitin ligase, is overexpressed in CRPCs. Its overexpression promoted androgen-independent cell growth. In this funding period we determined the role of TRAF4 and its regulated AR targeted genes in CRPC cell growth. We found that TRAF4 promoted AR recruitment to these gene enhancers to promote CRPC development. We further identified TRAF4-mediated AR ubiquitination sites.