Drosophila melanogaster SL2 cells contain a hypoxically inducible DNA binding complex which recognises mammalian HIF-binding sites.
Nuclear extracts from Drosophila SL2 cells were found to contain a hypoxically inducible complex capable of binding to hypoxia response elements from mammalian genes. This complex (HIF-D) resembled mammalian hypoxia inducible factor (HIF-1) in DNA sequence specificity, abrogation of induction by cycloheximide, induction by desferrioxamine and redox sensitivity of DNA binding. However, HIF-D was not induced by cobalt and was less sensitive to phosphatase than HIF-1. Endogenous phosphoglycerate kinase mRNA in SL2 cells showed similar inducible characteristics to HIF-D. These findings are evidence that the mammalian HIF-1 dependent system of oxygen regulated gene expression has a functional homologue in Drosophila.
Nagao
M
M
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Ebert
B L
BL
Ratcliffe
P J
PJ
Pugh
C W
CW
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015687:Cell Hypoxia; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010735:Phosphoglycerate Kinase / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D014157:Transcription Factors
D015342:DNA Probes; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D003035:Cobalt; D003513:Cycloheximide; D010735:Phosphoglycerate Kinase; D010744:Phosphoric Monoester Hydrolases; D003676:Deferoxamine; D004229:Dithiothreitol