FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor

David Lando, Daniel J. Peet, Jeffrey J. Gorman, Dean A. Whelan, Murray L. Whitelaw, Richard K. Bruick

Research output: Contribution to journalArticle

1056 Scopus citations

Abstract

Mammalian cells adapt to hypoxic conditions through a transcriptional response pathway mediated by the hypoxia-inducible factor, HIF. HIF transcriptional activity is suppressed under normoxic conditions by hydroxylation of an asparagine residue within its C-terminal transactivation domain, blocking association with coactivators. Here we show that the protein FIH-1, previously shown to interact with HIF, is an asparaginyl hydroxylase. Like known hydroxylase enzymes, FIH-1 is an Fe(II)-dependent enzyme that uses molecular O2 to modify its substrate. Together with the recently discovered prolyl hydroxylases that regulate HIF stability, this class of oxygen-dependent enzymes comprises critical regulatory components of the hypoxic response pathway.

Original languageEnglish (US)
Pages (from-to)1466-1471
Number of pages6
JournalGenes and Development
Volume16
Issue number12
DOIs
StatePublished - Jun 15 2002

Keywords

  • Asparaginyl hydroxylase
  • HIF
  • Hypoxia
  • Oxygen sensing

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002). FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes and Development, 16(12), 1466-1471. https://doi.org/10.1101/gad.991402