Abstract
The hypoxia-inducible factors (HIFs) are critical for cellular adaptation to limiting oxygen and regulate a wide array of genes when cued by cellular oxygen-sensing mechanisms. HIF is able to direct transcription from either of two transactivation domains, each of which is regulated by distinct mechanisms. The oxygen-dependent asparaginyl hydroxylase factor-inhibiting HIF-1α (FIH-1) is a key regulator of the HIF C-terminal transactivation domain, and provides a direct link between oxygen sensation and HIF-mediated transcription. Additionally, there are phosphorylation and nitrosylation events reported to modulate HIF transcriptional activity, as well as numerous transcriptional coactivators and other interacting proteins that together provide cell and tissue specificity of HIF target gene regulation.
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Abbreviations
- 2-OG:
-
2-oxoglutarate
- ARD:
-
ankyrin-repeat domain
- Arnt1:
-
aryl hydrocarbon receptor nuclear translocator
- bHLH:
-
basic helix–loop–helix
- CAD:
-
C-terminal transactivation domain
- CBP:
-
Creb-binding protein
- CH1 domain:
-
cysteine/histidine-rich domain 1
- EPO:
-
erythropoietin
- FIH-1:
-
factor-inhibiting HIF-1α
- HBS:
-
HIF-binding site
- HIF:
-
hypoxia-inducible factor
- HRE:
-
hypoxia response elements
- Hsp90:
-
heat-shock protein 90
- IPAS:
-
inhibitory PAS domain protein
- NAD:
-
N-terminal transactivation domain
- ODDD:
-
oxygen-dependent degradation domain
- PAS:
-
Per-Arnt-Sim homology
- PHD:
-
prolyl hydroxylase domain
- SUMO:
-
small ubiquitin-like modifier
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Acknowledgements
We thank the members of the Peet laboratory for reviewing the manuscript; Anne Chapman-Smith for assistance with preparation of the figures and the Australian Research Council, National Health and Medical Research Council of Australia and the Cancer Council of South Australia for financial support.
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Lisy, K., Peet, D. Turn me on: regulating HIF transcriptional activity. Cell Death Differ 15, 642–649 (2008). https://doi.org/10.1038/sj.cdd.4402315
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DOI: https://doi.org/10.1038/sj.cdd.4402315
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