Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha

Biochem Biophys Res Commun. 1998 Aug 28;249(3):811-6. doi: 10.1006/bbrc.1998.9234.


Hypoxia inducible factor-1 (HIF-1) is a heterodimeric complex of two basic-helix-loop-helix proteins of the PAS family which is critical for oxygen-dependent expression of many mammalian genes. Regulation is mediated by the alpha subunit (HIF-1 alpha) and sequences from HIF-1 alpha can confer hypoxia-inducible activity on a Ga14 fusion protein. To analyse conservation of this system of gene regulation between Drosophila and mammalian cells we constructed Ga14 fusions with a series of Drosophila basic-helix-loop-helix PAS (bHLH-PAS) proteins and tested for hypoxia inducibility in transfected Hep3B cells. We found that Ga14 functions with Similar (Sima) but not other Drosophila bHLH-PAS proteins showed inducible activity following exposure to stimuli which classically activate mammalian HIF-1:hypoxia, cobaltous ions, and desferrioxamine. We also found that Sima protein accumulated in Drosophila SL2 cells following hypoxia. Together these findings indicate the existence of functional homologies between Sima and HIF-1 alpha, and that conservation is such as to enable Sima to interact with the hypoxia signal transduction system in mammalian cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia / genetics
  • Cell Hypoxia / physiology
  • Cell Line
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins*
  • Gene Expression Regulation
  • Genes, Insect
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Insect Proteins / chemistry
  • Insect Proteins / genetics*
  • Insect Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Oxygen / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Species Specificity
  • Transcription Factors*
  • Transcriptional Activation
  • Transfection


  • DNA-Binding Proteins
  • Drosophila Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Insect Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Sima protein, Drosophila
  • Transcription Factors
  • Oxygen