The Von Hippel-Lindau (VHL) protein is a substrate recognition component of an E3 ubiquitin ligase complex containing elongin BC (TCEB1 and TCEB2), cullin 1 (CUL1), and RING-box protein 1 (RBX1). The ability of VHL to block Elongin function may play a role in normal cell growth regulation. The product of the VHL gene has multiple reported functions, the best characterized of which is its role as the recognition component of an ubiquitin E3 ligase complex responsible for mediating oxygen-dependent destruction of hypoxia-inducible factor-alpha (HIFalpha) subunits. Interactions with elongin BC, RPB1, RPB7 and the pVHLassociated KRAB-A domain containing protein (VHLaK) suggest that VHL may also play a more direct role in transcriptional repression.
