HIFα targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing

Mircea Ivan, K. Kondo, H. Yang, W. Kim, J. Valiando, M. Ohh, A. Salic, J. M. Asara, W. S. Lane, Jr Kaelin W.G.

Research output: Contribution to journalArticle

3270 Citations (Scopus)

Abstract

HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe2+, this protein modification may play a key role in mammalian oxygen sensing.

Original languageEnglish (US)
Pages (from-to)464-468
Number of pages5
JournalScience
Volume292
Issue number5516
StatePublished - Apr 20 2001
Externally publishedYes

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Hydroxylation
Proline
Oxygen
Von Hippel-Lindau Tumor Suppressor Protein
Peptides
Ubiquitin-Protein Ligases
Transcription Factors
Hypoxia
Proteins

ASJC Scopus subject areas

  • General

Cite this

Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., ... Kaelin W.G., J. (2001). HIFα targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science, 292(5516), 464-468.

HIFα targeted for VHL-mediated destruction by proline hydroxylation : Implications for O2 sensing. / Ivan, Mircea; Kondo, K.; Yang, H.; Kim, W.; Valiando, J.; Ohh, M.; Salic, A.; Asara, J. M.; Lane, W. S.; Kaelin W.G., Jr.

In: Science, Vol. 292, No. 5516, 20.04.2001, p. 464-468.

Research output: Contribution to journalArticle

Ivan, M, Kondo, K, Yang, H, Kim, W, Valiando, J, Ohh, M, Salic, A, Asara, JM, Lane, WS & Kaelin W.G., J 2001, 'HIFα targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing', Science, vol. 292, no. 5516, pp. 464-468.
Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M et al. HIFα targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science. 2001 Apr 20;292(5516):464-468.
Ivan, Mircea ; Kondo, K. ; Yang, H. ; Kim, W. ; Valiando, J. ; Ohh, M. ; Salic, A. ; Asara, J. M. ; Lane, W. S. ; Kaelin W.G., Jr. / HIFα targeted for VHL-mediated destruction by proline hydroxylation : Implications for O2 sensing. In: Science. 2001 ; Vol. 292, No. 5516. pp. 464-468.
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AU - Asara, J. M.

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