The VHL Tumor Suppressor: Riding Tandem with GSK3β in Primary Cilium Maintenance

Claudio R. Thoma, Ian J. Frew and Wilhelm Krek

volume 6 | issue 15

1 August 2007
Pages: 1809 - 1813

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Amongst other clinical manifestations, patients with the von Hippel-Lindau (VHL) cancer syndrome are predisposed to develop kidney cysts, which are considered to be precursor lesions of clear cell renal cell carcinoma (ccRCC). Recent evidence has highlighted an unexpected function of the VHL tumour suppressor protein (pVHL) in maintaining the structural integrity of the primary cilium, a microtubule-based cellular antenna important for suppression of uncontrolled proliferation of kidney epithelial cells and cyst formation. Intriguingly, this function of pVHL is directly linked to its capacity to regulate the microtubule cytoskeleton independent of its well-characterized role in the degradation of hypoxia inducible factor alpha (HIFα) subunits. However, loss of pVHL alone does not suffice for a cell to lose the primary cilium. Other pathways need to be additionally inactivated, including one involving glycogen synthase kinase 3 beta (GSK3β). These new findings draw attention to a primary cilium-maintenance network as new territory for pVHL tumour suppressive activity and have implications for understanding the development of kidney pathology in the setting of VHL disease.

Authors

Claudio R. Thoma

Institute of Cell Biology and Life Science Zurich Graduate School; Zurich, Switzerland

Ian J. Frew

Institute of Cell Biology; Zurich, Switzerland

Wilhelm Krek