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

Genes and Development - Tập 16 Số 12 - Trang 1466-1471 - 2002
David Lando1, Daniel J. Peet2, Jeffrey J. Gorman3, Dean A. Whelan3, Murray L. Whitelaw2, Richard K. Bruick4
1Department of Molecular BioSciences (Biochemistry) and the Centre for the Molecular Genetics of Development, Adelaide University SA 5005, Australia.
2University of Adelaide
3CSIRO,
4Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9152, USA

Tóm tắt

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.

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Genes and Development

Tập 16 Số 12

1466-1471

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