title: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.
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.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287-3914, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Wang
authors.forename: B H
authors.initials: BH
authors.lastname: Jiang
authors.forename: E A
authors.initials: EA
authors.lastname: Rue
authors.forename: G L
authors.initials: GL
authors.lastname: Semenza
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015687:Cell Hypoxia; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000302:isolation & purification; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000302:isolation & purification; D010100:Oxygen / Q000737:chemistry*; D012313:RNA / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D012313:RNA; D010100:Oxygen