title: The caspase-8 homolog Dredd cleaves Imd and Relish but is not inhibited by p35.
abstract: In Drosophila, the Imd pathway is activated by diaminopimelic acid-type peptidoglycan and triggers the humoral innate immune response, including the robust induction of antimicrobial peptide gene expression. Imd and Relish, two essential components of this pathway, are both endoproteolytically cleaved upon immune stimulation. Genetic analyses have shown that these cleavage events are dependent on the caspase-8 like Dredd, suggesting that Imd and Relish are direct substrates of Dredd. Among the seven Drosophila caspases, we find that Dredd uniquely promotes Imd and Relish processing, and purified recombinant Dredd cleaves Imd and Relish in vitro. In addition, interdomain cleavage of Dredd is not required for Imd or Relish processing and is not observed during immune stimulation. Baculovirus p35, a suicide substrate of executioner caspases, is not cleaved by purified Dredd in vitro. Consistent with this biochemistry but contrary to earlier reports, p35 does not interfere with Imd signaling in S2* cells or in vivo.
authors.affiliation: From the Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Chan-Hee
authors.initials: CH
authors.lastname: Kim
authors.affiliation: From the Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Donggi
authors.initials: D
authors.lastname: Paik
authors.affiliation: From the Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Florentina
authors.initials: F
authors.lastname: Rus
authors.affiliation: From the Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605 Neal.Silverman@umassmed.edu.
authors.forename: Neal
authors.initials: N
authors.lastname: Silverman
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D053181:Caspase 8 / Q000378:metabolism; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004330:Drosophila / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D011994:Recombinant Proteins; C101626:Rel protein, Drosophila; D014157:Transcription Factors; D014764:Viral Proteins; C439909:imd protein, Drosophila; C492234:p35 protein, Baculovirus; D053181:Caspase 8; D020169:Caspases; C431887:dredd protein, Drosophila
keywords: Caspase; Dredd; Drosophila; Imd; Innate Immunity; Insect Immunity; NF-κB; Relish; p35