PMID- 9731218 OWN - NLM STAT- MEDLINE DCOM- 19981002 LR - 20131121 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 249 IP - 3 DP - 1998 Aug 28 TI - Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha. PG - 811-6 AB - 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. FAU - Bacon, N C AU - Bacon NC AD - Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom. FAU - Wappner, P AU - Wappner P FAU - O'Rourke, J F AU - O'Rourke JF FAU - Bartlett, S M AU - Bartlett SM FAU - Shilo, B AU - Shilo B FAU - Pugh, C W AU - Pugh CW FAU - Ratcliffe, P J AU - Ratcliffe PJ LA - eng GR - Wellcome Trust/United Kingdom PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (DNA-Binding Proteins) RN - 0 (Drosophila Proteins) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Insect Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Sima protein, Drosophila) RN - 0 (Transcription Factors) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Cell Hypoxia/genetics/physiology MH - Cell Line MH - DNA-Binding Proteins/chemistry/*genetics/metabolism MH - Drosophila/*genetics/metabolism MH - *Drosophila Proteins MH - Gene Expression Regulation MH - Genes, Insect MH - Humans MH - Hypoxia-Inducible Factor 1 MH - Hypoxia-Inducible Factor 1, alpha Subunit MH - Insect Proteins/chemistry/*genetics/metabolism MH - Nuclear Proteins/*genetics/metabolism MH - Oxygen/metabolism MH - Recombinant Fusion Proteins/genetics/metabolism MH - Signal Transduction MH - Species Specificity MH - *Transcription Factors MH - Transcriptional Activation MH - Transfection EDAT- 1998/09/10 00:00 MHDA- 1998/09/10 00:01 CRDT- 1998/09/10 00:00 PHST- 1998/09/10 00:00 [pubmed] PHST- 1998/09/10 00:01 [medline] PHST- 1998/09/10 00:00 [entrez] AID - S0006-291X(98)99234-8 [pii] AID - 10.1006/bbrc.1998.9234 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1998 Aug 28;249(3):811-6. doi: 10.1006/bbrc.1998.9234.