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Nat Cell Biol. 2000 Jul;2(7):423-7.

Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein.

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1
Department of Medicine, Brigham and Womens Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome that is characterized by the development of multiple vascular tumors and is caused by inactivation of the von Hippel-Lindau protein (pVHL). Here we show that pVHL, through its beta-domain, binds directly to hypoxia-inducible factor (HIF), thereby targeting HIF for ubiquitination in an alpha-domain-dependent manner. This is the first function to be ascribed to the pVHL beta-domain. Furthermore, we provide the first direct evidence that pVHL has a function analogous to that of an F-box protein, namely, to recruit substrates to a ubiquitination machine. These results strengthen the link between overaccumulation of HIF and development of VHL disease.

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PMID:
10878807
DOI:
10.1038/35017054
[Indexed for MEDLINE]
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