Einzeltreffer — DigiBib

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.

Titel:	NLRC3, a member of the NLR family of proteins, is a negative regulator of innate immune signaling induced by the DNA sensor STING.
Autor/in / Beteiligte Person:	Zhang, L ; Mo, J ; Swanson, KV ; Wen, H ; Petrucelli, A ; Gregory, SM ; Zhang, Z ; Schneider, M ; Jiang, Y ; Fitzgerald, KA ; Ouyang, S ; Liu, ZJ ; Damania, B ; Shu, HB ; Duncan, JA ; Ting, JP
Link:	Zum Volltext
Zeitschrift:	Immunity, Jg. 40 (2014-03-20), Heft 3, S. 329
Veröffentlichung:	Cambridge, MA : Cell Press ; <i>Original Publication</i>: Cambridge, Mass. : Cell Press, c1994-, 2014
Medientyp:	academicJournal
ISSN:	1097-4180 (electronic)
DOI:	10.1016/j.immuni.2014.01.010
Schlagwort:	Animals Cell Line Cyclic GMP analogs & derivatives Cyclic GMP pharmacology Cytokines biosynthesis Herpes Simplex immunology Herpes Simplex metabolism Herpesvirus 1, Human physiology Humans Intercellular Signaling Peptides and Proteins deficiency Interferon Type I biosynthesis Mice Mice, Knockout Protein Binding Protein Serine-Threonine Kinases metabolism Protein Transport DNA immunology Immunity, Innate Intercellular Signaling Peptides and Proteins genetics Intercellular Signaling Peptides and Proteins metabolism Membrane Proteins metabolism Signal Transduction
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Immunity] 2014 Mar 20; Vol. 40 (3), pp. 329-41. <i>Date of Electronic Publication: </i>2014 Feb 20. MeSH Terms: Immunity, Innate* ; Signal Transduction* ; DNA / immunology ; Intercellular Signaling Peptides and Proteins / genetics ; Intercellular Signaling Peptides and Proteins / metabolism ; Membrane Proteins / metabolism ; Animals ; Cell Line ; Cyclic GMP / analogs & derivatives ; Cyclic GMP / pharmacology ; Cytokines / biosynthesis ; Herpes Simplex / immunology ; Herpes Simplex / metabolism ; Herpesvirus 1, Human / physiology ; Humans ; Intercellular Signaling Peptides and Proteins / deficiency ; Interferon Type I / biosynthesis ; Mice ; Mice, Knockout ; Protein Binding ; Protein Serine-Threonine Kinases / metabolism ; Protein Transport Comments: Comment in: Immunity. 2014 Mar 20;40(3):305-6. 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(PMID: 18559423) Grant Information: R01 CA156330 United States CA NCI NIH HHS; P01 DK094779 United States DK NIDDK NIH HHS; R01 AI088255 United States AI NIAID NIH HHS; U19AI1099665 United States AI NIAID NIH HHS; R37-AI029564 United States AI NIAID NIH HHS; CA156330 United States CA NCI NIH HHS; AI088255 United States AI NIAID NIH HHS; R37 AI029564 United States AI NIAID NIH HHS; R01 DE018281 United States DE NIDCR NIH HHS; T32 CA009156 United States CA NCI NIH HHS; AI107810 United States AI NIAID NIH HHS; U19 AI109965 United States AI NIAID NIH HHS; P01DK094779 United States DK NIDDK NIH HHS; U19 AI107810 United States AI NIAID NIH HHS; U54 AI057157 United States AI NIAID NIH HHS Substance Nomenclature: 0 (Cytokines) ; 0 (Intercellular Signaling Peptides and Proteins) ; 0 (Interferon Type I) ; 0 (Membrane Proteins) ; 0 (NLRC3 protein, mouse) ; 0 (Sting1 protein, mouse) ; 61093-23-0 (bis(3',5')-cyclic diguanylic acid) ; 9007-49-2 (DNA) ; EC 2.7.1.- (Tbk1 protein, mouse) ; EC 2.7.11.1 (Protein Serine-Threonine Kinases) ; H2D2X058MU (Cyclic GMP) Entry Date(s): Date Created: 20140225 Date Completed: 20140515 Latest Revision: 20211203 Update Code: 20231215 PubMed Central ID: PMC4011014

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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.