Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the β-carbon of asparagine-803
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Asparagine-803 in the C-terminal transactivation domain of human hypoxia-inducible factor (HIF)-1 α-subunit is hydroxylated by factor inhibiting HIF-1 (FIH-1) under normoxic conditions causing abrogation of the HIF-1α/p300 interaction. NMR and other analyses of a hydroxylated HIF fragment produced in vitro demonstrate that hydroxylation occurs at the β-carbon of Asn-803 and imply production of the threo-isomer, in contrast with other known aspartic acid/asparagine hydroxylases that produce the erythro-isomer.
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Hypoxia encourages interaction between C-TAD and CBP/p300 through inhibition of oxygen-dependent hydroxylation of N803, resulting in transcriptional activation of target genes.
“Alternatively, hypoxia encourages this interaction through the inhibition of oxygen dependent hydroxylation of N803, resulting in transcriptional activation of the target genes32, 33, 34.”
From HIF-1α pathway: role, regulation and intervention for cancer therapy (2015) · cites this paper as [34]
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- Authors
- McNEILL, L. A., HEWITSON, K. S., CLARIDGE, T. D., SEIBEL, J. F., HORSFALL, L. E., & SCHOFIELD, C. J.
- Affiliations
- University of Oxford (GB)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2002-11-01
- Volume
- 367
- Issue
- 3
- Pages
- 571-575
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1222951
- OpenAlex
- W1999204839
- Cited by
- 215
- References
- 29
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 13 · 2022: 12 · 2021: 12 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 11 · 2016: 7 · 2015: 6 · 2014: 8 · 2013: 7 · 2012: 7
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- European Commission
- Directorate for Biological Sciences
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- FIH-1, asparaginyl hydroxylase, hypoxia-inducible factor-1α, HIF-1α, threo isomer, C-terminal transactivation domain, normoxic conditions
- MeSH terms
- Amino Acid Sequence, Asparagine, Carbon, Catalysis, DNA-Binding Proteins, Hydroxylation, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Transcription Factors, Nuclear Magnetic Resonance, Biomolecular, Hypoxia-Inducible Factor 1
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