Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel
Author: ["Michael Ohh","Cheol Won Park","Mircea Ivan","Michael A. Hoffman","Tae-You Kim","L. Eric Huang","Nikola Pavletich","Vincent Chau","William G. Kaelin"]
Publication: Nature Cell Biology
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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 β-domain, binds directly to hypoxia-inducible factor (HIF), thereby targeting HIF for ubiquitination in an α-domain-dependent manner. This is the first function to be ascribed to the pVHL β-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.
Cite this article
Ohh, M., Park, C., Ivan, M. et al. Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel–Lindau protein. Nat Cell Biol 2, 423–427 (2000). https://doi.org/10.1038/35017054
