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 underlying mechanism for TRAF4-promoted AR transcriptional activity on a different set of genes, which leads to androgen-independent growth. We also generated prostate-specific TRAF4 overexpression mouse strain to facilitate the study on the role of TRAF4 in CRPC development in vivo.