Reference - Detail
|Author||Tsuda M, Langmann C, Harden N, Aigaki T.|
|Title||The RING-finger scaffold protein Plenty of SH3s targets TAK1 to control immunity signalling in Drosophila.|
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.
|MeSH||Animals Carrier Proteins / genetics* Carrier Proteins / immunology Cell Line Cytoskeletal Proteins / genetics* Cytoskeletal Proteins / immunology Drosophila / genetics* Drosophila / immunology Drosophila Proteins / genetics* Drosophila Proteins / immunology Feedback, Physiological Female Gene Expression Regulation / immunology Gene Silencing JNK Mitogen-Activated Protein Kinases / immunology JNK Mitogen-Activated Protein Kinases / metabolism Lipopolysaccharides MAP Kinase Kinase Kinases / genetics* MAP Kinase Kinase Kinases / immunology Male Mutation Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / immunology Phosphoprotein Phosphatases / genetics Phosphoprotein Phosphatases / immunology RNA / metabolism Signal Transduction / immunology Time Factors Transcription Factors / genetics Transcription Factors / immunology Transfection Ubiquitin-Protein Ligases / genetics* Ubiquitin-Protein Ligases / metabolism|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY|