Beyond the hypoxia-inducible factor-centric tumour suppressor model of von Hippel-Lindau.
OBJECTIVE
To provide an overview of the recent advances in the understanding of the molecular mechanisms governing the tumour suppressor functions of the von Hippel-Lindau protein.


RESULTS
von Hippel-Lindau is a vital component of an E3 ubiquitin ligase complex involved in the oxygen-dependent targeting of hypoxia-inducible factor for ubiquitin-mediated destruction. Recent reports have linked von Hippel-Lindau to the regulation of diverse biological processes including cell adhesion, extracellular matrix assembly and ciliogenesis in a manner dependent and/or independent of hypoxia-inducible factor.


CONCLUSIONS
The tumour suppressor function of von Hippel-Lindau has remained hypoxia-inducible factor-centric since the discovery of von Hippel-Lindau as a bona fide negative regulator of the ubiquitous oxygen-sensing pathway. Emerging evidence supports this hypothesis with the elucidation of fundamental cellular processes deregulated upon the inactivation of the von Hippel-Lindau-hypoxia-inducible factor pathway, but has also proved compelling on the hypoxia-inducible factor-independent tumour suppressor role of von Hippel-Lindau. These and continuing studies into the molecular pathways and mechanisms governing the tumour suppressor functions of von Hippel-Lindau will ultimately afford new avenues for anticancer strategies for the improved treatment of a diverse array of cancers.
Roberts
Andrew M
AM
Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
Ohh
Michael
M
D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008954:Models, Biological; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism*; D006623:von Hippel-Lindau Disease / Q000378:metabolism
D015820:Cadherins; D051177:Catenins; D051793:Hypoxia-Inducible Factor 1; D051794:Von Hippel-Lindau Tumor Suppressor Protein