The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
| Autor: | Osamu Hitotsumatsu, Sophia Chai, Marcia Chien, Regina Celeste Ahmad, Matthew T. Wheeler, Paula J. Hurley, David L. Boone, Emre E. Turer, Colleen Tsui, Elizabeth M. McNally, Eric Lee, Cecile M. Pickart, Averil Ma |
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| Rok vydání: | 2004 |
| Předmět: |
Lipopolysaccharides
Immunology Receptors Cell Surface Receptors Tumor Necrosis Factor Proinflammatory cytokine Deubiquitinating enzyme Mice Ubiquitin immune system diseases Antigens CD hemic and lymphatic diseases Immunology and Allergy Animals Transcription factor Tumor Necrosis Factor alpha-Induced Protein 3 TNF Receptor-Associated Factor 6 Toll-like receptor Innate immune system Membrane Glycoproteins biology Tumor Necrosis Factor-alpha Macrophages Toll-Like Receptors Intracellular Signaling Peptides and Proteins NF-kappa B Nuclear Proteins Proteins Molecular biology Shock Septic Mice Inbred C57BL Cysteine Endopeptidases Receptors Tumor Necrosis Factor Type I biology.protein Tumor necrosis factor alpha Signal Transduction |
| Zdroj: | Nature immunology. 5(10) |
| ISSN: | 1529-2908 |
| Popis: | A20 is a cytoplasmic protein required for the termination of tumor necrosis factor (TNF)-induced signals. We show here that mice doubly deficient in either A20 and TNF or A20 and TNF receptor 1 developed spontaneous inflammation, indicating that A20 is also critical for the regulation of TNF-independent signals in vivo. A20 was required for the termination of Toll-like receptor-induced activity of the transcription factor NF-kappaB and proinflammatory gene expression in macrophages, and this function protected mice from endotoxic shock. A20 accomplished this biochemically by directly removing ubiquitin moieties from the signaling molecule TRAF6. The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells. |
| Databáze: | OpenAIRE |
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