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

1014 Citations (Scopus)

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

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Mixed Function Oxygenases
Enzymes
Prolyl Hydroxylases
Asparagine
Hydroxylation
Transcriptional Activation
Oxygen
Hypoxia
Proteins

Keywords

  • Asparaginyl hydroxylase
  • HIF
  • Hypoxia
  • Oxygen sensing

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

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

FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. / Lando, David; Peet, Daniel J.; Gorman, Jeffrey J.; Whelan, Dean A.; Whitelaw, Murray L.; Bruick, Richard K.

In: Genes and Development, Vol. 16, No. 12, 15.06.2002, p. 1466-1471.

Research output: Contribution to journalArticle

Lando, D, Peet, DJ, Gorman, JJ, Whelan, DA, Whitelaw, ML & Bruick, RK 2002, 'FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor', Genes and Development, vol. 16, no. 12, pp. 1466-1471. https://doi.org/10.1101/gad.991402
Lando, David ; Peet, Daniel J. ; Gorman, Jeffrey J. ; Whelan, Dean A. ; Whitelaw, Murray L. ; Bruick, Richard K. / FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. In: Genes and Development. 2002 ; Vol. 16, No. 12. pp. 1466-1471.
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