Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway

• Published in: The EMBO journal Vol. 24; no. 19; pp. 3423 - 3434
• Main Authors: Kleino, Anni, Valanne, Susanna, Ulvila, Johanna, Kallio, Jenni, Myllymäki, Henna, Enwald, Heidi, Stöven, Svenja, Poidevin, Mickael, Ueda, Ryu, Hultmark, Dan, Lemaitre, Bruno, Rämet, Mika
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 05.10.2005; Blackwell Publishing Ltd
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Amino Acid Sequence; Animals; antimicrobial peptide expression; Base Sequence; Blotting, Western; Cells, Cultured; DNA - genetics; DNA Primers; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - immunology; Drosophila melanogaster - microbiology; Drosophila melanogaster/genetics/immunology/microbiology; Drosophila Proteins - genetics; Drosophila Proteins - immunology; Drosophila Proteins - metabolism; Drosophila Proteins/genetics/immunology/metabolism; E coli; Electrophoresis, Polyacrylamide Gel; Escherichia coli - immunology; Gene Library; Immunohistochemistry; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Inhibitor of Apoptosis Proteins/genetics/metabolism; innate immunity; Insect Proteins - metabolism; Luciferases; Mammals; Models, Biological; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNAi screen; Sequence Analysis, DNA; Signal Transduction - genetics; Signal Transduction - immunology; Signal Transduction/genetics/immunology; signaling; Western; Polyacrylamide Gel; DNA; Electrophoresis; Cultured; Models; Biological; Sequence Analysis; Blotting; Adaptor Proteins; Cells; Signal Transducing/genetics/metabolism
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7600807

The Imd signaling cascade, similar to the mammalian TNF‐receptor pathway, controls antimicrobial peptide expression in Drosophila. We performed a large‐scale RNAi screen to identify novel components of the Imd pathway in Drosophila S2 cells. In all, 6713 dsRNAs from an S2 cell‐derived cDNA library were analyzed for their effect on Attacin promoter activity in response to Escherichia coli. We identified seven gene products required for the Attacin response in vitro, including two novel Imd pathway components: inhibitor of apoptosis 2 (Iap2) and transforming growth factor‐activated kinase 1 (TAK1)‐binding protein (TAB). Iap2 is required for antimicrobial peptide response also by the fat body in vivo. Both these factors function downstream of Imd. Neither TAB nor Iap2 is required for Relish cleavage, but may be involved in Relish nuclear localization in vitro, suggesting a novel mode of regulation of the Imd pathway. Our results show that an RNAi‐based approach is suitable to identify genes in conserved signaling cascades.