Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha.
Hypoxia inducible factors (HIFs) are heterodimeric transcription factors that regulate a number of adaptive responses to low oxygen tension. They are composed of alpha- and beta-subunits that belong to the basic helix-loop-helix-PAS (bHLH-PAS) superfamily. In our efforts to identify new bHLH-PAS proteins, we cloned a cDNA encoding a novel alpha-class ... hypoxia inducible factor, HIF3alpha. The HIF3alpha open reading frame encodes a 662-amino acid protein with a predicted molecular weight of 73 kDa and is expressed in adult thymus, lung, brain, heart, and kidney. The N-terminal bHLH-PAS domain of this protein shares amino acid sequence identity with that of HIF1alpha and HIF2alpha (57% and 53% identity, respectively). The C-terminus of HIF3alpha contains a 36-amino acid sequence that shares 61% identity with the hypoxia responsive domain-1 (HRD1) of HIF1alpha. In transient transfections, this domain confers hypoxia responsiveness when linked to a heterologous transactivation domain. In vitro studies reveal that HIF3alpha dimerizes with a prototype beta-class subunit, ARNT, and that the resultant heterodimer recognizes the hypoxia responsive element (HRE) core sequence, TACGTG. Transient transfection experiments demonstrate that the HIF3alpha-ARNT interaction can occur in vivo, and that the activity of HIF3alpha is upregulated in response to cobalt chloride or low oxygen tension.
Mesh Terms:
Amino Acid Sequence, Animals, Basic Helix-Loop-Helix Transcription Factors, Chromosomes, Human, Pair 9, Cloning, Molecular, Conserved Sequence, DNA-Binding Proteins, Databases, Factual, Enhancer Elements, Genetic, Helix-Loop-Helix Motifs, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular Sequence Data, Nuclear Proteins, Recombinant Proteins, Transcription Factors, Transfection, Up-Regulation
Amino Acid Sequence, Animals, Basic Helix-Loop-Helix Transcription Factors, Chromosomes, Human, Pair 9, Cloning, Molecular, Conserved Sequence, DNA-Binding Proteins, Databases, Factual, Enhancer Elements, Genetic, Helix-Loop-Helix Motifs, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular Sequence Data, Nuclear Proteins, Recombinant Proteins, Transcription Factors, Transfection, Up-Regulation
Gene Expr.
Date: Dec. 05, 1998
PubMed ID: 9840812
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