Insights into the Role of the von Hippel-Lindau Gene Product

Abstract

Many adaptive responses to hypoxia involve changes in gene transcription mediated by the hypoxia-inducible factor 1 complex. Central to this is oxygen-dependent proteolysis of the α subunit, which has recently been shown to require the von Hippel-Lindau tumour-suppressor protein. This observation provides one mechanism by which inherited defects in the von Hippel-Lindau gene could cause features of the clinical syndrome, and offers insight into the events leading to sporadic clear cell renal cancer. Furthermore, it clearly implicates the von Hippel-Lindau tumour-suppressor protein in the biochemistry of oxygen sensing.