The Role of the Small Ubiquitin-Related Modifier (SUMO) Pathway in Prostate Cancer

Abstract: SUMO (small ubiquitin-related modifier) conjugation is a reversible three-step process of protein post-translational modifications mediating protein-protein interactions, subcellular compartmentalization and regulation of transcriptional events. Among divergent transcription factors regulated by SUMOylation and deSUMOylation, the androgen receptor (AR) is of exceptional significance, given its established role in prostate carcinogenesis. The enzymes of the SUMO pathway can have diverse effects on AR transcriptional activity, either via direct modification of the AR or through modification of AR co-regulators. Accumulating in vitro and in vivo evidence implicates the SUMO pathway in AR-dependent signaling. Prostate cancer cell proliferation and hypoxia-induced angiogenesis are also regulated by the SUMO pathway, through an AR-independent mechanism. Thus, an important role has been revealed for members of the SUMO pathway in prostate cancer (PCa) development and progression, offering new therapeutic targets.