title: The role of von Hippel-Lindau tumor suppressor protein and hypoxia in renal clear cell carcinoma.
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.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A8.
authors.forename: Roxana I
authors.initials: RI
authors.lastname: Sufan
authors.forename: Michael A S
authors.initials: MA
authors.lastname: Jewett
authors.forename: Michael
authors.initials: M
authors.lastname: Ohh
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000503:physiopathology*; D015687:Cell Hypoxia; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D009154:Mutation; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000494:pharmacology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics* / Q000503:physiopathology
chemical_list: D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human