The VHL (von Hippel–Lindau) tumour-suppressor gene is inactivated in VHL disease and in sporadic cases of CCRCC [clear-cell RCC (renal cell carcinoma)]. pVHL (VHL protein) functions as part of an E3 ubiquitin ligase complex that targets proteins for proteasomal degradation. The best-characterized substrate is HIF-α (hypoxia-inducible factor-α). Loss of pVHL and subsequent up-regulation of HIF target genes has been attributed to the highly vascular nature of these neoplasms. However, pVHL does not just function as the executioner of HIF-α. Additional functions of pVHL that may be important in preventing CCRCC tumorigenesis have been identified, including primary cilium maintenance, assembly of the extracellular matrix and roles in the stabilization of p53 and Jade-1 (gene for apoptosis and differentiation in epithelia). Current evidence indicates that pVHL probably requires additional co-operating signalling pathways for CCRCC initiation and tumorigenesis.
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June 2008
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Conference Article|
May 21 2008
Role of the VHL (von Hippel–Lindau) gene in renal cancer: a multifunctional tumour suppressor
Michelle J. Nyhan;
Michelle J. Nyhan
*Leslie C. Quick Laboratory, Cork Cancer Research Centre, University College Cork, Cork, Ireland
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Gerald C. O'Sullivan;
Gerald C. O'Sullivan
†Mercy University Hospital, Grenville Place, Cork, Ireland
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Sharon L. McKenna
Sharon L. McKenna
1
*Leslie C. Quick Laboratory, Cork Cancer Research Centre, University College Cork, Cork, Ireland
1To whom correspondence should be addressed (email s.mckenna@ucc.ie).
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Biochem Soc Trans (2008) 36 (3): 472–478.
Article history
Received:
February 18 2008
Citation
Michelle J. Nyhan, Gerald C. O'Sullivan, Sharon L. McKenna; Role of the VHL (von Hippel–Lindau) gene in renal cancer: a multifunctional tumour suppressor. Biochem Soc Trans 1 June 2008; 36 (3): 472–478. doi: https://doi.org/10.1042/BST0360472
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