The Drosophila Ubiquitin-Specific Protease dUSP36/Scny Targets IMD to Prevent Constitutive Immune Signaling
| Autor: | Jacques Baudier, Elodie Engel, Amélie Avet-Rochex, Marie Gottar, Marie-Odile Fauvarque, Emmanuel Taillebourg, Hervé Tricoire, Evelyne Bergeret, Christelle Benaud, Dominique Thevenon |
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| Rok vydání: | 2009 |
| Předmět: |
Proteases
Cancer Research MICROBIO Gene Dosage Repressor Biology Microbiology Immune system Ubiquitin Virology Immunology and Microbiology(all) Endopeptidases Gram-Negative Bacteria Protein Interaction Mapping Animals Drosophila Proteins Germ-Free Life Gene Silencing MOLIMMUNO Molecular Biology Innate immune system JNK Mitogen-Activated Protein Kinases NF-kappa B Cell biology Gene Expression Regulation Proteasome Biochemistry biology.protein Drosophila Parasitology CELLBIO Signal transduction Signal Transduction Deubiquitination |
| Zdroj: | Cell Host & Microbe. 6(4):309-320 |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2009.09.007 |
| Popis: | Summary Ubiquitin proteases remove ubiquitin monomers or polymers to modify the stability or activity of proteins and thereby serve as key regulators of signal transduction. Here, we describe the function of the Drosophila ubiquitin-specific protease 36 (dUSP36) in negative regulation of the immune deficiency (IMD) pathway controlled by the IMD protein. Overexpression of catalytically active dUSP36 ubiquitin protease suppresses fly immunity against Gram-negative pathogens. Conversely, silencing dUsp36 provokes IMD-dependent constitutive activation of IMD-downstream Jun kinase and NF-κB signaling pathways but not of the Toll pathway. This deregulation is lost in axenic flies, indicating that dUSP36 prevents constitutive immune signal activation by commensal bacteria. dUSP36 interacts with IMD and prevents K63-polyubiquitinated IMD accumulation while promoting IMD degradation in vivo. Blocking the proteasome in dUsp36 -expressing S2 cells increases K48-polyubiquitinated IMD and prevents its degradation. Our findings identify dUSP36 as a repressor whose IMD deubiquitination activity prevents nonspecific activation of innate immune signaling. |
| Databáze: | OpenAIRE |
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