Abstract

Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins. HIF-1 alpha is most closely related to Sim. HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. HIF-1 alpha and HIF-1 beta (ARNT) RNA and protein levels were induced in cells exposed to 1% O2 and decayed rapidly upon return of the cells to 20% O2, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia.

Keywords

Aryl hydrocarbon receptor nuclear translocatorBasic helix-loop-helixPAS domainBiologyEnhancerHypoxia-Inducible Factor 1Cell biologyMolecular biologyG alpha subunitTranscription factorMediatorAlpha (finance)Alpha helixGeneChemistryProtein structureBiochemistryDNA-binding proteinProtein subunitMedicine

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Publication Info

Year
1995
Type
article
Volume
92
Issue
12
Pages
5510-5514
Citations
6119
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G L Wang, Bing‐Hua Jiang, E A Rue et al. (1995). Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.. Proceedings of the National Academy of Sciences , 92 (12) , 5510-5514. https://doi.org/10.1073/pnas.92.12.5510

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DOI
10.1073/pnas.92.12.5510