Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension

Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4. doi: 10.1073/pnas.92.12.5510.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Hypoxia*
  • DNA, Complementary
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / isolation & purification
  • Helix-Loop-Helix Motifs
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / isolation & purification
  • Oxygen / chemistry*
  • RNA / genetics
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry*
  • Transcription Factors / isolation & purification
  • Tumor Cells, Cultured

Substances

  • DNA, Complementary
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Transcription Factors
  • RNA
  • Oxygen

Associated data

  • GENBANK/L19872
  • GENBANK/M19020
  • GENBANK/M30114
  • GENBANK/M31067
  • GENBANK/M34070
  • GENBANK/M69238
  • GENBANK/U22431
  • GENBANK/X13945
  • GENBANK/X55666
  • GENBANK/Z23066