title: The RING-finger scaffold protein Plenty of SH3s targets TAK1 to control immunity signalling in Drosophila.
abstract: Imd-mediated innate immunity is activated in response to infection by Gram-negative bacteria and leads to the activation of Jun amino-terminal kinase (JNK) and Relish, a nuclear factor-kappaB transcription factor responsible for the expression of antimicrobial peptides. Plenty of SH3s (POSH) has been shown to function as a scaffold protein for JNK activation, leading to apoptosis in mammals. Here, we report that POSH controls Imd-mediated immunity signalling in Drosophila. In POSH-deficient flies, JNK activation and Relish induction were delayed and sustained, which indicated that POSH is required for properly timed activation and termination of the cascade. The RING finger of POSH, possessing ubiquitin-ligase activity, was essential for termination of JNK activation. We show that POSH binds to and degrades TAK1, a crucial activator of both the JNK and the Relish signalling pathways. These results establish a novel role for POSH in the Drosophila immune system.
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji-shi, Tokyo 192-0397, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tsuda
authors.forename: Caillin
authors.initials: C
authors.lastname: Langmann
authors.forename: Nicholas
authors.initials: N
authors.lastname: Harden
authors.forename: Toshiro
authors.initials: T
authors.lastname: Aigaki
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000276:immunology; D004330:Drosophila / Q000235:genetics* / Q000276:immunology; D029721:Drosophila Proteins / Q000235:genetics* / Q000276:immunology; D025461:Feedback, Physiological; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D020868:Gene Silencing; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000276:immunology; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000276:immunology; D012313:RNA / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D009419:Nerve Tissue Proteins; D010749:Phosphoprotein Phosphatases; D012313:RNA; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D000099151:MAP Kinase Kinase Kinase 7; C488990:AttA protein, Drosophila; C054756:DptA protein, Drosophila; C453299:POSH protein, Drosophila; C101626:Rel protein, Drosophila; C110854:puc protein, Drosophila