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 language | English (US) |
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Pages (from-to) | 1466-1471 |
Number of pages | 6 |
Journal | Genes and Development |
Volume | 16 |
Issue number | 12 |
DOIs | |
State | Published - Jun 15 2002 |
Keywords
- Asparaginyl hydroxylase
- HIF
- Hypoxia
- Oxygen sensing
ASJC Scopus subject areas
- General Medicine