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  • Title: The role of von Hippel-Lindau tumor suppressor protein and hypoxia in renal clear cell carcinoma.
    Author: Sufan RI, Jewett MA, Ohh M.
    Journal: Am J Physiol Renal Physiol; 2004 Jul; 287(1):F1-6. PubMed ID: 15180922.
    Abstract:
    The majority of kidney cancers are caused by the mutation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL protein (pVHL) is part of an E3 ubiquitin ligase complex called VEC that is composed of elongin B, elongin C, cullin 2, NEDD8, and Rbx1. VEC targets a hypoxia-inducible factor (HIF) transcription factor for ubiquitin-mediated destruction selectively in the presence of oxygen. In the absence of wild-type pVHL, as in VHL patients or in the majority of sporadic clear cell renal cell carcinomas, HIF-responsive genes are inappropriately activated even under normoxia. Recent insights into the molecular mechanisms regulating the function of pVHL, and thereby HIF, in the context of kidney cancer are the focus of this review.
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