title: Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge.
abstract: The Drosophila defense against pathogens largely relies on the activation of two signaling pathways: immune deficiency (IMD) and Toll. The IMD pathway is triggered mainly by Gram-negative bacteria, whereas the Toll pathway responds predominantly to Gram-positive bacteria and fungi. The activation of these pathways leads to the rapid induction of numerous NF-κB-induced immune response genes, including antimicrobial peptide genes. The IMD pathway shows significant similarities with the TNF receptor pathway. Recent evidence indicates that the IMD pathway is also activated in response to various noninfectious stimuli (i.e., inflammatory-like reactions). To gain a better understanding of the molecular machinery underlying the pleiotropic functions of this pathway, we first performed a comprehensive proteomics analysis to identify the proteins interacting with the 11 canonical members of the pathway initially identified by genetic studies. We identified 369 interacting proteins (corresponding to 291 genes) in heat-killed Escherichia coli-stimulated Drosophila S2 cells, 92% of which have human orthologs. A comparative analysis of gene ontology from fly or human gene annotation databases points to four significant common categories: (i) the NuA4, nucleosome acetyltransferase of H4, histone acetyltransferase complex, (ii) the switching defective/sucrose nonfermenting-type chromatin remodeling complex, (iii) transcription coactivator activity, and (iv) translation factor activity. Here we demonstrate that sumoylation of the IκB kinase homolog immune response-deficient 5 plays an important role in the induction of antimicrobial peptide genes through a highly conserved sumoylation consensus site during bacterial challenge. Taken together, the proteomics data presented here provide a unique avenue for a comparative functional analysis of proteins involved in innate immune reactions in flies and mammals.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Equipe Avenir, 67084 Strasbourg, France. hidehiro.fukuyama@riken.jp
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Fukuyama
authors.forename: Yann
authors.initials: Y
authors.lastname: Verdier
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Guan
authors.forename: Chieko
authors.initials: C
authors.lastname: Makino-Okamura
authors.forename: Victoria
authors.initials: V
authors.lastname: Shilova
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Elie
authors.initials: E
authors.lastname: Maksoud
authors.forename: Jun
authors.initials: J
authors.lastname: Matsubayashi
authors.forename: Iman
authors.initials: I
authors.lastname: Haddad
authors.forename: Kerstin
authors.initials: K
authors.lastname: Spirohn
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Ono
authors.forename: Charles
authors.initials: C
authors.lastname: Hetru
authors.forename: Jean
authors.initials: J
authors.lastname: Rossier
authors.forename: Trey
authors.initials: T
authors.lastname: Ideker
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
authors.forename: Joëlle
authors.initials: J
authors.lastname: Vinh
authors.forename: Jules A
authors.initials: JA
authors.lastname: Hoffmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000276:immunology; D004330:Drosophila / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology; D017344:Genes, Insect; D051548:Histone Acetyltransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D060066:Protein Interaction Maps; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D029721:Drosophila Proteins; D051548:Histone Acetyltransferases
keywords: IMD interactome; functional proteomics; small ubiquitin-like modifier