Molecular Basis of the von Hippel-Lindau Cancer Syndrome
Wilhelm Krek, Institute of Cell Biology, ETH Zurich, 8093 Zurich, Switzerland
Despite their rarity, inherited cancer syndromes are of tremendous biological importance. Investigations of the specific mutations responsible for these syndromes and the cellular signalling pathways disrupted by the mutant proteins have provided unprecedented insight into the molecular origins and pathogenesis of inherited and sporadic forms of cancer and have helped greatly to illuminate the molecular basis of fundamental biological processes. Studies of the von Hippel Lindau (VHL) tumor suppressor gene, whose inactivation plays a causal role in hereditary and sporadic renal cancer, illustrate this principle very well. Work over the last years has advanced our understanding of the molecular mechanisms underlying the tumor suppressor functions of the VHL gene product VHL. It is now widely appreciated that VHL acts to destabilise hypoxia-inducible factor HIF, a key effector of the hypoxia signalling pathway. However, growing evidence indicates that tumour suppression by VHL also involves the control of a wide variety of HIF-independent processes. The lecture highlighted recent progress on the roles of VHL in primary cilium maintenance and suppression of renal cyst formation and promotion of chromosome stability.
