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von Hippel-Lindau: A Tumor Suppressor Links Microtubules to Ciliogenesis and Cancer Development

¹ Renal Division, University Hospital Freiburg, Freiburg, Germany and ² Department of Medicine IV, University of Cologne, Cologne, Germany

Requests for reprints: Thomas Benzing, Department of Medicine IV, University of Cologne, Kerpener Strasse 62, D-50924 Köln, Germany. Phone: 49-221-478-4480; Fax: 49-221-478-5959; E-mail: thomas.benzing{at}uk-koeln.de.

Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic renal cell carcinoma. The tumor suppressor role of the protein pVHL is based on its ability to target transcription factors of the hypoxia-inducible factor family for degradation, but other functions of pVHL are less clearly defined. New findings show that pVHL is necessary for cilia formation. pVHL interacts with PAR proteins, a complex that specifies the membrane domains of polarized epithelial cells, and directs the orientation of growing microtubules. Loss of pVHL results in aberrant orientation of newly formed microtubules and prevents ciliogenesis. These results add to a growing body of evidence linking cilia and the cell cycle and suggest that the tumor suppressor role of pVHL may involve previously unrecognized pathways. [Cancer Res 2007;67(10):4537–40]

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