FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor
Commonwealth Scientific and Industrial Research Organisation · Health Sciences and Nutrition · +3 more institutions
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 O(2) to modify its substrate. Together with the recently discovered prolyl hydroxylases that regulate HIF stability, this class of oxygen-dependent enzymes comprises critical regulatory…
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- References
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Authors
6- DLDavid LandoCorresponding
Commonwealth Scientific and Industrial Research Organisation, Health Sciences and Nutrition, Centre for Cancer Biology, The University of Adelaide, The University of Texas Southwestern Medical Center
- DJDaniel J. Peet
Commonwealth Scientific and Industrial Research Organisation, Health Sciences and Nutrition, The University of Adelaide, The University of Texas Southwestern Medical Center
- JJJeffrey J. Gorman
Commonwealth Scientific and Industrial Research Organisation, Health Sciences and Nutrition, The University of Adelaide, The University of Texas Southwestern Medical Center
- DADean A. Whelan
Commonwealth Scientific and Industrial Research Organisation, Health Sciences and Nutrition, The University of Adelaide, The University of Texas Southwestern Medical Center
- MLMurray L. Whitelaw
Commonwealth Scientific and Industrial Research Organisation, Health Sciences and Nutrition, The University of Adelaide, The University of Texas Southwestern Medical Center
Topics & keywords
- Transactivation
- Biology
- Hydroxylation
- Enzyme
- Asparagine
- Biochemistry
- Transcription factor
- Hypoxia-inducible factors