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

Michael Ohh, Cheol Won Park, Mircea Ivan, Michael A. Hoffman, Tae You Kim, L. Eric Huang, Nikola Pavletich, Vincent Chau, William G. Kaelin

Research output: Contribution to journalArticle

1094 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)423-427
Number of pages5
JournalNature Cell Biology
Volume2
Issue number7
DOIs
StatePublished - Oct 30 2000

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Ubiquitination
von Hippel-Lindau Disease
Hereditary Neoplastic Syndromes
F-Box Proteins
Proteins
Blood Vessels
Hypoxia
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Ohh, M., Park, C. W., Ivan, M., Hoffman, M. A., Kim, T. Y., Huang, L. E., ... Kaelin, W. G. (2000). Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel - Lindau protein. Nature Cell Biology, 2(7), 423-427. https://doi.org/10.1038/35017054
Ohh, Michael ; Park, Cheol Won ; Ivan, Mircea ; Hoffman, Michael A. ; Kim, Tae You ; Huang, L. Eric ; Pavletich, Nikola ; Chau, Vincent ; Kaelin, William G. / Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel - Lindau protein. In: Nature Cell Biology. 2000 ; Vol. 2, No. 7. pp. 423-427.
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Ohh, M, Park, CW, Ivan, M, Hoffman, MA, Kim, TY, Huang, LE, Pavletich, N, Chau, V & Kaelin, WG 2000, 'Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel - Lindau protein', Nature Cell Biology, vol. 2, no. 7, pp. 423-427. https://doi.org/10.1038/35017054

Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel - Lindau protein. / Ohh, Michael; Park, Cheol Won; Ivan, Mircea; Hoffman, Michael A.; Kim, Tae You; Huang, L. Eric; Pavletich, Nikola; Chau, Vincent; Kaelin, William G.

In: Nature Cell Biology, Vol. 2, No. 7, 30.10.2000, p. 423-427.

Research output: Contribution to journalArticle

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