The von Hippel-Lindau tumor suppressor gene.

Abstract	Germline mutations of the von Hippel-Lindau tumor suppressor gene (VHL) in humans causes a hereditary cancer syndrome characterized by the development of retinal and central nervous system hemangioblastomas. Other tumors associated with von Hippel-Lindau disease include clear cell renal carcinomas and pheochromocytomas. Tumor development in this setting is due to functional loss of the remaining wild-type VHL allele. Biallelic VHL inactivation is also common in nonhereditary hemangioblastomas and clear cell renal carcinomas, in keeping with Knudson's 2-Hit Model of carcinogenesis. The VHL gene product, pVHL, is a component of an E3 ubiquitin ligase that targets the alpha subunits of the HIF (hypoxia-inducible factor) transcription factor for destruction in the presence of oxygen. Consequently, tumor cells lacking pVHL overproduce the products of HIF target genes such as vascular endothelial growth factor and transforming growth factor alpha. pVHL has been implicated in a variety of processes that are central to carcinogenesis including cell-cycle control, differentiation, extracellular matrix formation and turnover, and angiogenesis.
Authors	K Kondo, W G Kaelin Jr
Journal	Experimental cell research (Exp Cell Res) Vol. 264 Issue 1 Pg. 117-25 (Mar 10 2001) ISSN: 0014-4827 [Print] United States
PMID	11237528 (Publication Type: Journal Article, Review)
Copyright	Copyright 2001 Academic Press.
Chemical References	DNA-Binding Proteins HIF1A protein, human Hif1a protein, mouse Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Macromolecular Substances Nuclear Proteins Proteins Transcription Factors Tumor Suppressor Proteins Ubiquitin-Protein Ligases Von Hippel-Lindau Tumor Suppressor Protein Ligases VHL protein, human
Topics	Animals DNA-Binding Proteins (metabolism) Disease Models, Animal Female Gene Deletion Genes, Tumor Suppressor Humans Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Ligases Macromolecular Substances Male Mice Models, Biological Mutation Neoplasms (genetics) Nuclear Proteins (metabolism) Proteins (genetics, metabolism, physiology) Transcription Factors Tumor Suppressor Proteins Ubiquitin-Protein Ligases Von Hippel-Lindau Tumor Suppressor Protein von Hippel-Lindau Disease (diagnosis, genetics)

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