Mutation of the von Hippel-Lindau tumor supressor (VHL) is associated with the majority of renal carcinomas and also with VHL syndrome. In the cell, VHL regulates the degradation of HIF-1 and the levels of vascular angiogenic growth factor (VEGF-1).
The crystal structure of the ternary complex of VHL with ElonginB and ElonginC, shown here, revealed how mutations in VHL may compromise its function. It suggested structural and functional homology between VHL and the F-box adaptor protein of the SCF complex, which is involved in regulation of several cell-cycle proteins by ubiquitin-mediated proteolysis.
