Reference - Detail
|Author||Kleino A, Valanne S, Ulvila J, Kallio J, Myllymäki H, Enwald H, Stöven S, Poidevin M, Ueda R, Hultmark D, Lemaitre B, Rämet M.|
|Title||Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway.|
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.
|MeSH||Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism Amino Acid Sequence Animals Base Sequence Blotting, Western Cells, Cultured DNA / genetics DNA Primers Drosophila Proteins / genetics* Drosophila Proteins / immunology Drosophila Proteins / metabolism* Drosophila melanogaster / genetics* Drosophila melanogaster / immunology Drosophila melanogaster / microbiology Electrophoresis, Polyacrylamide Gel Escherichia coli / immunology Gene Library Immunohistochemistry Inhibitor of Apoptosis Proteins / genetics* Inhibitor of Apoptosis Proteins / metabolism Insect Proteins / metabolism Luciferases Models, Biological Molecular Sequence Data Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction RNA Interference Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA Signal Transduction / genetics* Signal Transduction / immunology|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY|