Regulation of Androgen Receptor by E3 Ubiquitin Ligases: for More or Less

Bo Li, Wenfu Lu, Zhenbang Chen


Prostate cancer (PCa) primarily depends on androgen receptor (AR) signaling pathway for the initiation and growth as well as recurrence after castration [1]. Androgen deprivation therapy (ADT) effectively alleviates the symptoms of the malignancy to arrest further growth of the primary tumors or the progression of metastasis in patients with the advanced PCa. However, the relapse occurs in many patients after a short period, and PCa cells eventually become insensitive to ADT - termed castration resistant prostate cancer [2, 3].  Tremendous advancements have been achieved to decipher the mechanisms on AR signaling, and ubiquitination machinery contributes to PCa directly or indirectly by either promotion of AR transcriptional activity or degradation of AR protein levels. The recent report reveals that SKP2 is an E3 ubiquitin ligase for AR protein, and SKP2 levels determine AR expression through ubiquitin-mediated proteasomal degradation.  Given the pivotal roles of AKT and SKP2 in cancers, the differential mechanisms of AR ubiquitination by various E3 ligases hold valuable significance and beneficial implications for PCa control.



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