Affiliation:
1. From the Howard Hughes Medical Institute, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Abstract
Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene causes the von Hippel-Lindau hereditary cancer syndrome, and somatic mutations of this gene have been linked to the development of sporadic hemangioblastomas and clear-cell renal carcinomas. The VHL tumor suppressor protein (pVHL), through its oxygen-dependent polyubiquitylation of hypoxia-inducible factor (HIF), plays a central role in the mammalian oxygen-sensing pathway. This interaction between pVHL and HIF is governed by post-translational prolyl hydroxylation of HIF in the presence of oxygen by a conserved family of Egl-nine (EGLN) enzymes. In the absence of pVHL, HIF becomes stabilized and is free to induce the expression of its target genes, many of which are important in regulating angiogenesis, cell growth, or cell survival. Moreover, preliminary data indicate that HIF plays a critical role in pVHL-defective tumor formation, raising the possibility that drugs directed against HIF or its downstream targets (such as vascular endothelial growth factor) might one day play a role in the treatment of hemangioblastoma and renal cell carcinoma. On the other hand, clear genotype-phenotype correlations are emerging in VHL disease and can be rationalized if pVHL has functions separate from its control of HIF.
Publisher
American Society of Clinical Oncology (ASCO)
Reference176 articles.
1. Collins E: Intra-ocular growths (two cases, brother and sister, with peculiar vascular new growth, probably retinal, affecting both eyes). Trans Ophthalmol Soc U K 14:141,1894-149,
2. Über eine sehr seltene Erkrankung der Netzhaut
3. Lindau A: Zur frage der angiomatosis retinai und ihrer hirncomplikation. Acta Ophthalmol 4:193,1927-226,
4. Davison C, Brock S, Cyke CG: Retinal and central nervous hemangioblastomatosis with visceral changes (von Hippel-Lindau's disease). Bull Neurol Inst New York 5:72,1936-93,
5. von Hippel-Lindau Disease
Cited by
801 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献