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

3182 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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