The von Hippel-Lindau tumor suppressor gene
- PMID: 11237528
- DOI: 10.1006/excr.2000.5139
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.
Copyright 2001 Academic Press.
Similar articles
-
von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF.Hum Mol Genet. 2001 May 1;10(10):1019-27. doi: 10.1093/hmg/10.10.1019. Hum Mol Genet. 2001. PMID: 11331612
-
Up-regulation of hypoxia-inducible factors HIF-1alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function.Oncogene. 2000 Nov 16;19(48):5435-43. doi: 10.1038/sj.onc.1203938. Oncogene. 2000. PMID: 11114720
-
Identification of cyclin D1 and other novel _targets for the von Hippel-Lindau tumor suppressor gene by expression array analysis and investigation of cyclin D1 genotype as a modifier in von Hippel-Lindau disease.Cancer Res. 2002 Jul 1;62(13):3803-11. Cancer Res. 2002. PMID: 12097293
-
The von Hippel-Lindau tumor suppressor gene and kidney cancer.Clin Cancer Res. 2004 Sep 15;10(18 Pt 2):6290S-5S. doi: 10.1158/1078-0432.CCR-sup-040025. Clin Cancer Res. 2004. PMID: 15448019 Review.
-
Von Hippel-Lindau tumor suppressor protein and hypoxia-inducible factor in kidney cancer.Am J Nephrol. 2004 Jan-Feb;24(1):1-13. doi: 10.1159/000075346. Epub 2003 Dec 3. Am J Nephrol. 2004. PMID: 14654728 Review.
Cited by
-
The Roles of Angiogenesis in Malignant Melanoma: Trends in Basic Science Research over the Last 100 Years.ISRN Oncol. 2012;2012:546927. doi: 10.5402/2012/546927. Epub 2012 Jun 7. ISRN Oncol. 2012. PMID: 22720169 Free PMC article.
-
KRAS, A Prime Mediator in Pancreatic Lipid Synthesis through Extra Mitochondrial Glutamine and Citrate Metabolism.Int J Mol Sci. 2021 May 11;22(10):5070. doi: 10.3390/ijms22105070. Int J Mol Sci. 2021. PMID: 34064761 Free PMC article. Review.
-
[Von-Hippel-Lindau gene mutation types. Association of gene expression signatures in clear cell renal cell carcinoma].Pathologe. 2008 Nov;29 Suppl 2:303-7. doi: 10.1007/s00292-008-1031-1. Pathologe. 2008. PMID: 18751980 German.
-
Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer.J Cell Mol Med. 2010 Apr;14(4):771-94. doi: 10.1111/j.1582-4934.2009.00994.x. Epub 2009 Dec 8. J Cell Mol Med. 2010. PMID: 20015196 Free PMC article. Review.
-
Epigenetic mechanisms and the hallmarks of cancer: an intimate affair.Am J Cancer Res. 2020 Jul 1;10(7):1954-1978. eCollection 2020. Am J Cancer Res. 2020. PMID: 32774995 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
