The zinc metalloprotease STAM-binding protein-like 1 (STAMBPL1) has been identified as a deubiquitinase by specifically cleaving Lys-63-linked polyubiquitin chains, but its cellular function remains unclear. Here we described the potential role of STAMBPL1 in suppression of the intrinsic apoptosis. We observed substantially high amounts of STAMBPL1 proteins in androgen-independent prostate cancer PC3 and DU145 cell lines. STAMBPL1 RNAi depletion triggered caspase-3/-7-dependent apoptosis in PC3 and DU145 cells. STAMBPL1 knockdown-induced apoptosis was accompanied by accumulation of cellular ROS and a decrease in endogenous caspase inhibitor XIAP protein content. Treatment cells with antioxidant NAC delayed STAMBPL1 silencing-induced apoptosis, whereas ectopic expression of XIAP almost completely abrogated apoptosis. We further elucidated that STAMBPL1 knockdown diverted XIAP protein to lysosomal degradation pathway. Taken together, these studies show that STAMBPL1 depletion induces apoptosis by promoting XIAP lysosomal degradation, and suggest that targeting deubiquitinase STAMBPL1 might offer promising therapeutic strategy for prostate cancer.
Keywords: Deubiquitination; Inhibitor of apoptosis proteins; Lysosomal degradation; Proteasome.
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