Together , our results suggest that hsRPB 7 is a downstream target of the VHL ubiquitylating complex and pVHL may regulate angiogenesis by targeting hsRPB 7 for degradation via the ubiquitylation pathway and preventing VEGF expression . . ^^^ Here , we report that the pVHL can directly bind to the human RNA polymerase 2 seventh subunit ( hsRPB 7 ) through its beta domain , and naturally occurring beta domain mutations can decrease the binding of pVHL to hsRPB 7 . ^^^ Introducing wild type pVHL into human kidney tumor cell lines carrying endogenous mutant non functional pVHL facilitates ubiquitylation and proteasomal degradation of hsRPB 7 , and decreases its nuclear accumulation . pVHL can also suppress hsRPB 7 induced VEGF promoter transactivation , mRNA expression and VEGF protein secretion . ^^^ |