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Gene Review

hif-1  -  Protein HIF-1

Caenorhabditis elegans

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Disease relevance of hif-1

  • This complex consists of HIF-1 and AHA-1, which are encoded by C. elegans homologs of the hypoxia-inducible factor (HIF) alpha and beta subunits, respectively. hif-1 mutants exhibit no severe defects under standard laboratory conditions, but they are unable to adapt to hypoxia [1].
  • HSP72 upregulation in AC hif-1 mutants was also observed; however, it was insufficient to improve heat/stress tolerance, suggesting that HIF-1 upregulation is essential for acclimation, whereas HSP72 upregulation in the absence of HIF-1 is inadequate [2].

High impact information on hif-1


Biological context of hif-1

  • To understand and describe more fully the molecular basis for hypoxia response in this important genetic model system, we compared hypoxia-induced changes in mRNA expression in wild-type, hif-1-deficient, and vhl-1-deficient C. elegans using whole genome microarrays [3].
  • Some gene groups up-regulated in dauers and/or daf-2 were enriched for certain promoter elements as follows: the daf-16-binding element, the heat shock-response element, the heat shock-associated sequence, or the hif-1-response element [4].

Associations of hif-1 with chemical compounds

  • They validate this strategy by identifying two previously uncharacterized mutations: (1) tom-1, a mutation found in a forward genetic screen for enhanced acetylcholine secretion in Caenorhabditis elegans, and (2) an apparently spontaneous mutation in the hif-1 transcription factor gene [5].

Other interactions of hif-1

  • Although loss-of-function mutations in rhy-1 cause relatively modest increases in hif-1 mRNA and HIF-1 protein expression, some HIF-1 target genes are expressed at higher levels in rhy-1 mutants than in vhl-1 mutants [6].
  • Finally, several C. elegans genes, including hif-1 and egl-9, rendered C. elegans less susceptible to EPEC when mutated, suggesting their involvement in mediating toxin effects [7].


  1. The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia. Jiang, H., Guo, R., Powell-Coffman, J.A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  2. HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans. Treinin, M., Shliar, J., Jiang, H., Powell-Coffman, J.A., Bromberg, Z., Horowitz, M. Physiol. Genomics (2003) [Pubmed]
  3. Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans. Shen, C., Nettleton, D., Jiang, M., Kim, S.K., Powell-Coffman, J.A. J. Biol. Chem. (2005) [Pubmed]
  4. Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. McElwee, J.J., Schuster, E., Blanc, E., Thomas, J.H., Gems, D. J. Biol. Chem. (2004) [Pubmed]
  5. Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion. Dybbs, M., Ngai, J., Kaplan, J.M. PLoS Genet. (2005) [Pubmed]
  6. The Caenorhabditis elegans rhy-1 Gene Inhibits HIF-1 Hypoxia-Inducible Factor Activity in a Negative Feedback Loop That Does Not Include vhl-1. Shen, C., Shao, Z., Powell-Coffman, J.A. Genetics (2006) [Pubmed]
  7. Paralysis and killing of Caenorhabditis elegans by enteropathogenic Escherichia coli requires the bacterial tryptophanase gene. Anyanful, A., Dolan-Livengood, J.M., Lewis, T., Sheth, S., Dezalia, M.N., Sherman, M.A., Kalman, L.V., Benian, G.M., Kalman, D. Mol. Microbiol. (2005) [Pubmed]
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