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    NLRC3, a member of the NLR family of proteins, is a negative regulator of innate immune signaling induced by the DNA sensor STING

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    Authors
    Zhang, Lu
    Mo, Jinyao
    Swanson, Karen V.
    Wen, Haitao
    Petrucelli, Alex
    Gregory, Sean M.
    Zhang, Zhigang
    Schneider, Monika
    Jiang, Yan
    Fitzgerald, Katherine A.
    Ouyang, Songying
    Liu, Zhi-Jie
    Damania, Blossom
    Shu, Hong-Bing
    Duncan, Joseph A.
    Ting, Jenny P-Y
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    UMass Chan Affiliations
    Department of Medicine, Division of Infectious Diseases and Immunology
    Document Type
    Journal Article
    Publication Date
    2014-03-20
    Keywords
    Animals
    Cell Line
    Cyclic GMP
    Cytokines
    DNA
    Herpes Simplex
    Herpesvirus 1, Human
    Humans
    *Immunity, Innate
    Intercellular Signaling Peptides and Proteins
    Interferon Type I
    Membrane Proteins
    Mice
    Mice, Knockout
    Protein Binding
    Protein Transport
    Protein-Serine-Threonine Kinases
    *Signal Transduction
    Amino Acids, Peptides, and Proteins
    Bacteria
    Immunity
    Immunology and Infectious Disease
    Immunology of Infectious Disease
    Infectious Disease
    Nucleic Acids, Nucleotides, and Nucleosides
    Viruses
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    Link to Full Text
    http://dx.doi.org/10.1016/j.immuni.2014.01.010
    Abstract
    Stimulator of interferon genes (STING, also named MITA, MYPS, or ERIS) is an intracellular DNA sensor that induces type I interferon through its interaction with TANK-binding kinase 1 (TBK1). Here we found that the nucleotide-binding, leucine-rich-repeat-containing protein, NLRC3, reduced STING-dependent innate immune activation in response to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA viruses. NLRC3 associated with both STING and TBK1 and impeded STING-TBK1 interaction and downstream type I interferon production. By using purified recombinant proteins, we found NLRC3 to interact directly with STING. Furthermore, NLRC3 prevented proper trafficking of STING to perinuclear and punctated region, known to be important for its activation. In animals, herpes simplex virus 1 (HSV-1)-infected Nlrc3(-/-) mice exhibited enhanced innate immunity and reduced morbidity and viral load. This demonstrates the intersection of two key pathways of innate immune regulation, NLR and STING, to fine tune host response to intracellular DNA, DNA virus, and c-di-GMP.
    Source
    Immunity. 2014 Mar 20;40(3):329-41. doi: 10.1016/j.immuni.2014.01.010. Epub 2014 Feb 20. Link to article on publisher's site
    DOI
    10.1016/j.immuni.2014.01.010
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/34956
    PubMed ID
    24560620
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.immuni.2014.01.010
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