Journal
TRENDS IN MOLECULAR MEDICINE
Volume 10, Issue 9, Pages 466-472Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2004.07.008
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The proteolytic degradation of hypoxia inducible factor (HIF)alpha by the von Hippel-Lindau (VHL) tumour suppressor protein (pVHL) has emerged as a key cellular mechanism for the control of adaptive gene expression programmes in response to changes in oxygen levels. The inactivation of this mechanism is phenotypically depicted by the vascular nature of VHL-associated tumours and has also recently been associated with the processes of invasion and metastasis. However, the complex genotype-phenotype correlations, which are a hallmark of VHL disease, demonstrate that the function of pVHL is likely to extend beyond its crucial role in oxygen signal transduction and might include roles for pVHL in the regulation of microtubule dynamics, cell polarity and directed cell migration. Further studies aimed at defining the normal function of VHL in these processes will help to identify the molecular mechanisms underlying pVHL-associated tumourigenesis.
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