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Angiogenesis pp 181–191Cite as

Regulation of Angiogenesis by von Hippel Lindau Protein and HIF2

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von Hippel-Lindau (VHL) Syndrome is a rare, autosomal dominant, hereditary neoplastic disorder characterized by the development of hemangioblastomas, retinal angiomas and solid tumors in several organs. VHL-associated renal tumors are highly vascular, malignant and very often fatal. Affected individuals inherit an altered copy of the VHL tumor suppressor gene, and the wild type copy is later inactivated in somatic cells. VHL loss of function also occurs in the majority of sporadic cases of renal cell carcinoma. Thus, understanding the molecular basis of VHL syndrome has proven to be relevant to both patient populations. The VHL gene encodes the substrate recognition component (pVHL) of a ubiquitin ligase complex that targets hypoxia inducible factors (HIFs) for proteosome- mediated degradation in normoxic conditions. HIFs are ubiquitous transcriptional regulators that provide an essential oxygen sensing function. Failure to degrade HIFs, such as in hypoxia or in disease, results in the increased expression of a large collection of genes that regulate cellular energy metabolism, migration, proliferation and angiogenesis. In particular, because of its historic relevance to the pathogenesis of acute, chronic and inherited kidney diseases, the study of angiogenic regulation by the pVHL/HIF axis has contributed to fundamentally important advances in basic biology and medicine.

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Authors and Affiliations

  1. Center for Cancer Research, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, USA

    Donald P. Bottaro

  2. National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, USA

    Nelly Tan & W. Marston Linehan

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  1. Donald P. Bottaro
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  2. Nelly Tan
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Editors and Affiliations

  1. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    William D. Figg

  2. Department of Surgery Harvard Medical School and Vascular Biology Program, Children's Hospital Boston, Boston, MA, USA

    Judah Folkman

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Bottaro, D.P., Tan, N., Linehan, W.M. (2008). Regulation of Angiogenesis by von Hippel Lindau Protein and HIF2. In: Figg, W.D., Folkman, J. (eds) Angiogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71518-6_16

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