The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Role of VHL Gene Mutation in Human Cancer
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.
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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735
Self-citationHuang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113
Mutations of the VHL tumour suppressor gene in renal carcinoma
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Mutations in SDHD , a Mitochondrial Complex II Gene, in Hereditary Paraganglioma
Baysal, B. E., Ferrell, R. E., Willett-Brozick, J. E., Lawrence, E. C., Myssiorek, D., Bosch, A., Mey, A. V. D., Taschner, P. E. M., Rubinstein, W. S., Myers, E. N., et al. (2000) · Science · doi:10.1126/science.287.5454.848 · Cited by 1,638
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Self-citationAsparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558
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Ras, PI(3)K and mTOR signalling controls tumour cell growth
Shaw, R. J., & Cantley, L. C. (2006) · Nature · doi:10.1038/nature04869 · Cited by 2,019
Hypoxia signalling in cancer and approaches to enforce tumour regression
Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676
Shibata, T., Ohta, T., Tong, K. I., Kokubu, A., Odogawa, R., Tsuta, K., Asamura, H., Yamamoto, M., & Hirohashi, S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806268105 · Cited by 728
Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer
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Metadata
- Authors
- Kim, W. Y., & Kaelin, W. G.
- Venue
- Journal of Clinical Oncology
- Published
- 2004-12-15
- Volume
- 22
- Issue
- 24
- Pages
- 4991-5004
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2015644147
- Cited by
- 943
- References
- 27
- FWCI
- 18.24
- Type
- journal article
- Language
- en
- Open access
- closed
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