Mutations and loss of function of the Von Hippel-Lindau (VHL) tumor suppressor gene play a causal role in the pathogenesis of clear cell renal carcinomas (ccRCC), a pathological subtype that accounts for the majority kidney cancer each year. Mollapour work has shown that VHL ubiquitinates protein phosphatase-5 (PP5) for proteasomal degradation in a hypoxia- and prolyl-hydroxylation-independent manner. VHL-deficient ccRCC cell lines and patient tumors exhibit elevated PP5 levels. Downregulation of PP5 causes activation of the extrinsic apoptotic pathway in ccRCC cells, suggesting a prosurvival role for PP5 in kidney cancer.
Mollapour’s research group has been supported by grants from the National Institutes for General Medical Science and the National Cancer Institute to design and examine novel therapeutic strategies for patients with kidney, bladder and breast cancer.