Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O <sub>2</sub> -Regulated Prolyl Hydroxylation

DOI Web Site 被引用文献181件
  • Panu Jaakkola
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • David R. Mole
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • Ya-Min Tian
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • Michael I. Wilson
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • Janine Gielbert
    Michael Barber Centre for Mass Spectrometry, Department of Chemistry, University of Manchester Institute of Science and Technology, Manchester M60 1QD, UK.
  • Simon J. Gaskell
    Michael Barber Centre for Mass Spectrometry, Department of Chemistry, University of Manchester Institute of Science and Technology, Manchester M60 1QD, UK.
  • Alexander von Kriegsheim
    Glycobiology Institute, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
  • Holger F. Hebestreit
    Glycobiology Institute, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
  • Mridul Mukherji
    The Oxford Centre for Molecular Sciences and The Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QY, UK.
  • Christopher J. Schofield
    The Oxford Centre for Molecular Sciences and The Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QY, UK.
  • Patrick H. Maxwell
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • ‡ Christopher W. Pugh
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  • ‡ Peter J. Ratcliffe
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.

抄録

<jats:p>Hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-α subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel–Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. Here we show that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue (HIF-1α P564) by an enzyme we have termed HIF-α prolyl-hydroxylase (HIF-PH). An absolute requirement for dioxygen as a cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a cellular oxygen sensor.</jats:p>

収録刊行物

  • Science

    Science 292 (5516), 468-472, 2001-04-20

    American Association for the Advancement of Science (AAAS)

被引用文献 (181)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ