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Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Gothenburg, Sweden.
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
2015 (English)In: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 43, no 4, 647-659 p.Article in journal (Refereed) Published
Abstract [en]

Pattern-recognition receptors (PRRs) including Toll-like receptors, RIG-I-like receptors, and cytoplasmic DNA receptors are essential for protection against pathogens but require tight control to avert inflammatory diseases. The mechanisms underlying this strict regulation are unclear. MYSM1 was previously described as a key component of epigenetic signaling machinery. We found that in response to microbial stimuli, MYSM1 accumulated in the cytoplasm where it interacted with and inactivated TRAF3 and TRAF6 complexes to terminate PRR pathways for pro-inflammatory and type I interferon responses. Consequently, Mysm1 deficiency in mice resulted in hyper-inflammation and enhanced viral clearance but also susceptibility to septic shock. We identified two motifs in MYSM1 that were essential for innate immune suppression: the SWIRM domain that interacted with TRAF3 and TRAF6 and the metalloproteinase domain that removed K63 polyubiquitins. This study identifies MYSM1 as a key negative regulator of the innate immune system that guards against an overzealous self-destructive immune response.

Place, publisher, year, edition, pages
Elsevier, 2015. Vol. 43, no 4, 647-659 p.
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-111482DOI: 10.1016/j.immuni.2015.09.010ISI: 000363478700009PubMedID: 26474655OAI: oai:DiVA.org:umu-111482DiVA: diva2:877981
Available from: 2015-12-08 Created: 2015-11-13 Last updated: 2015-12-08Bibliographically approved

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Panda, SwarupaGekara, Nelson O.
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Molecular Infection Medicine Sweden (MIMS)Umeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Medicine)
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Immunity
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ReferencesLink to record
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