The von Hippel-Lindau tumour suppressor protein: new perspectives

von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by g ermline mutations of the VHL tumour suppressor gene. The VHL gene product, pVHL, forms multiprotein complexes that contain elongin B, elongin C and Cu l-2, and negatively regulates hypoxia-inducible mRNAs, pVHL is suspected to play a role in ubiquitination given the similarity of elongin C and Cul-2 with Skp1 and Cdc53, respectively, pVHL can also interact with fibronectin and is required for the assembly of a fibronectin matrix, Finally, pVHL, at least indirectly, plays a role in the ability of cells to exit the cell cy cle. Thus, pVHL is a tumour suppressor protein that regulates angiogenesis, extracellular matrix formation and the cell cycle.