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trim, cgas, pubmed, cells, dna, fig, article, infection, google, scholar, cas, ifnβ, activity, expression, virus, cell, central, mice, monoubiquitination, supplementary, cgamp, protein, showed, mrna, sensing, hsv, innate, bmdms, nature, cytosolic, production, pathway, immune, rna, response, immunity, data, stimulation, hekt, assay, cgasflag, role, domain, vitro, htdna, signaling, viral, shown, antiviral, ligase,

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nature portfolio privacy policy isre-ifnβ promoter-luciferase activity research advertising double-stranded dna-induced oligomerization ifnβ promoter-luciferase reporter c-terminal ncl1-ht2a-lin41 trim56-specific short-hairpin rnas social media middle panel rig-i-dependent sensing intracellular double-stranded dna mbp-cgas c-terminal region reprints thp1-lucia isg cells akt kinase-mediated checkpoint nature 458 nature 448 nature 498 nature 473 nature isreifnβ-lucia reporter genes c-terminal nhl domain29 double-stranded dna stimulation33 e3 ligase-dependent manner dual-glo luciferase assay suppress cgas-mediated innate sting-mediated dna sensing ifn-mediated antiviral pathway n-terminal ring domain serine/threonine protein kinases microbe-derived nucleic acids positive-strand rna alphavirus mediates dna binding increases dsdna-binding efficiency ion-trap mass spectrometry cgas-mediated dna sensing cyclic gmp-amp synthase individual protein–protein interactions35 bi-monthly mycoplasma screening thermo scientific tumor necrosis factor-α ifnβ promoter activity standard plaque-formation assay cgas-mediated ifnαβ production author information authors cgamp-mediated ifn responsiveness irf-3-dependent innate immunity wild-type cgas-flag

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      headline:TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing
      description:Intracellular nucleic acid sensors often undergo sophisticated modifications that are critical for the regulation of antimicrobial responses. Upon recognition of DNA, the cytosolic sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the second messenger cGAMP, which subsequently initiates downstream signaling to induce interferon-αβ (IFNαβ) production. Here we report that TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNαβ production to induce anti-DNA viral immunity. TRIM56 induces the Lys335 monoubiquitination of cGAS, resulting in a marked increase of its dimerization, DNA-binding activity, and cGAMP production. Consequently, TRIM56-deficient cells are defective in cGAS-mediated IFNαβ production upon herpes simplex virus-1 (HSV-1) infection. Furthermore, TRIM56-deficient mice show impaired IFNαβ production and high susceptibility to lethal HSV-1 infection but not to influenza A virus infection. This adds TRIM56 as a crucial component of the cytosolic DNA sensing pathway that induces anti-DNA viral innate immunity. The protein cGAS responds to the presence of cytosolic DNA by producing the second messenger cGAMP, which triggers antiviral interferon responses. Here, Seo et al. show that ubiquitination by the E3 ligase TRIM56 enhances cGAS activity and is important for the immune response against DNA viruses.
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