title: Hypoxia activates IKK-NF-κB and the immune response in Drosophila melanogaster.
abstract: Hypoxia, or low oxygen availability, is an important physiological and pathological stimulus for multicellular organisms. Molecularly, hypoxia activates a transcriptional programme directed at restoration of oxygen homoeostasis and cellular survival. In mammalian cells, hypoxia not only activates the HIF (hypoxia-inducible factor) family, but also additional transcription factors such as NF-κB (nuclear factor κB). Here we show that hypoxia activates the IKK-NF-κB [IκB (inhibitor of nuclear factor κB)-NF-κB] pathway and the immune response in Drosophila melanogaster. We show that NF-κB activation is required for organism survival in hypoxia. Finally, we identify a role for the tumour suppressor Cyld, as a negative regulator of NF-κB in response to hypoxia in Drosophila. The results indicate that hypoxia activation of the IKK-NF-κB pathway and the immune response is an important and evolutionary conserved response.
authors.affiliation: *Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bandarra
authors.affiliation: *Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: John
authors.initials: J
authors.lastname: Biddlestone
authors.affiliation: *Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: Sharon
authors.initials: S
authors.lastname: Mudie
authors.affiliation: †Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: H Arno
authors.initials: HA
authors.lastname: Muller
authors.affiliation: *Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors.forename: Sonia
authors.initials: S
authors.lastname: Rocha
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000074749:Deubiquitinating Enzyme CYLD; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics* / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D020672:I-kappa B Proteins / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins; C523258:CYLD protein, Drosophila; D000074749:Deubiquitinating Enzyme CYLD