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.
Highlights
Prostate cancer (PCa) is the most common cancer and the second leading cause of death from cancer in males in most western countries
SUMOylation depends upon the activity of small ubiquitin-related modifier (SUMO), a protein moiety that is conjugated to a specific lysine residue on target proteins [4]
Many questions remain unanswered with respect to the various roles played by SUMO
Summary
Prostate cancer (PCa) is the most common cancer and the second leading cause of death from cancer in males in most western countries. The transcriptional AR activity modulated by positive or negative regulators plays a critical role in controlling the growth and survival of PCa cells. Biomolecules 2012, 2 activity is essential for cancer cell growth because PCa, in most cases, will regress in response to androgen removal therapy [1,2]. SUMOylation depends upon the activity of small ubiquitin-related modifier (SUMO), a protein moiety that is conjugated to a specific lysine residue on target proteins [4]. Ubc catalyzes formation of an isopeptide bond between SUMO-1 and the ε-amino group of lysine in the target protein. SUMOylation typically occurs at a specific sequence, ψKXE, on the target protein where ψ is a hydrophobic residue and X is any amino acid. The multiple interconnections between members of the SUMO pathway, AR-mediated and AR-independent propagation of PCa are reviewed here, with implications for their ultimate clinical significance
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