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Proceedings of the National Academy of Sciences, Vol 92, 5510-5514, Copyright © 1995 by National Academy of Sciences

ARTICLE

Hypoxia-Inducible Factor 1 is a Basic-Helix-Loop-Helix-PAS Heterodimer Regulated by Cellular O2 Tension

GL Wang, B Jiang, EA Rue and GL Semenza

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-1ß is a series of ARNT gene products, which can thus heterodimerize with either HIF-1{alpha} or AHR. HIF-1{alpha} and HIF-1ß (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.
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