Journal article
Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines
Nature immunology, Vol.11(1), pp.70-75
01/2010
DOI: 10.1038/ni.1819
PMCID: PMC2872790
PMID: 19898473
Abstract
Balanced production of type I interferons and proinflammatory cytokines after engagement of Toll-like receptors (TLRs), which signal through adaptors containing a Toll-interleukin 1 receptor (TIR) domain, such as MyD88 and TRIF, has been proposed to control the pathogenesis of autoimmune disease and tumor responses to inflammation. Here we show that TRAF3, a ubiquitin ligase that interacts with both MyD88 and TRIF, regulated the production of interferon and proinflammatory cytokines in different ways. Degradative ubiquitination of TRAF3 during MyD88-dependent TLR signaling was essential for the activation of mitogen-activated protein kinases (MAPKs) and production of inflammatory cytokines. In contrast, TRIF-dependent signaling triggered noncanonical TRAF3 self-ubiquitination that activated the interferon response. Inhibition of degradative ubiquitination of TRAF3 prevented the expression of all proinflammatory cytokines without affecting the interferon response.
Details
- Title: Subtitle
- Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines
- Creators
- Atsushi Matsuzawa - Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Department of Pathology, School of Medicine, University of California San Diego Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, University of TokyoWeizhou Zhang - Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Department of Pathology, School of Medicine, University of California San DiegoPing-Hui Tseng - Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Department of Pathology, School of Medicine, University of California San Diego Institute of Biochemistry and Molecular Biology, National Yang-Ming UniversityTakashi Mino - Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Department of Pathology, School of Medicine, University of California San DiegoDario A A Vignali - Department of Immunology, St. Jude Children's Research HospitalMichael Karin - Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Department of Pathology, School of Medicine, University of California San Diego
- Resource Type
- Journal article
- Publication Details
- Nature immunology, Vol.11(1), pp.70-75
- DOI
- 10.1038/ni.1819
- PMID
- 19898473
- PMCID
- PMC2872790
- NLM abbreviation
- Nat Immunol
- ISSN
- 1529-2908
- eISSN
- 1529-2916
- Language
- English
- Date published
- 01/2010
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984083890102771
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