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1
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Antagonism of the STING pathway via activation of the AIM2 inflammasome by intracellular DNA
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1 Corrales, L., Woo, S.R., Williams, J.B., McWhirter, S.M., Dubensky, T.W. Jr., Gajewski, T.F., Antagonism of the STING pathway via activation of the AIM2 inflammasome by intracellular DNA. J Immunol 196 (2016), 3191–3198.
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Regulation of type I interferon responses
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3
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IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV
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3 Monroe, K.M., Yang, Z., Johnson, J.R., Geng, X., Doitsh, G., Krogan, N.J., Greene, W.C., IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV. Science 343 (2014), 428–432.
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4
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A cGAS-independent STING/IRF7 pathway mediates the immunogenicity of DNA vaccines
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4 Suschak, J.J., Wang, S., Fitzgerald, K.A., Lu, S., A cGAS-independent STING/IRF7 pathway mediates the immunogenicity of DNA vaccines. J Immunol 196 (2016), 310–316.
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Suschak, J.J.1
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Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies
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5 Lewinsohn, M., Brown, A.L., Weinel, L.M., Phung, C., Rafidi, G., Lee, M.K., Schreiber, A.W., Feng, J., Babic, M., Chong, C.E., et al. Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies. Blood 127 (2016), 1017–1023.
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Lewinsohn, M.1
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6
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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
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6 Freischmidt, A., Wieland, T., Richter, B., Ruf, W., Schaeffer, V., Muller, K., Marroquin, N., Nordin, F., Hubers, A., Weydt, P., et al. Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci 18 (2015), 631–636.
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7
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Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation
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7 Liu, S., Cai, X., Wu, J., Cong, Q., Chen, X., Li, T., Du, F., Ren, J., Wu, Y., Grishin, N., et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science, 2015.
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Liu, S.1
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8
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84923169931
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Suppression of systemic autoimmunity by the innate immune adaptor STING
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This paper uses lpr model of murine systemic autoimmunity to provide evidence that STING suppresses the TLR-induced innate signaling in systemic lupus erythematosus (SLE). Mechanistically, STING-deficient macrophages failed to express negative regulators of immune activation and thus were hyperresponsive to TLR ligands. These data describe STING as a key natural regulator of SLE, which can be manipulated to provide disease-specific therapeutics.
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8• Sharma, S., Campbell, A.M., Chan, J., Schattgen, S.A., Orlowski, G.M., Nayar, R., Huyler, A.H., Nundel, K., Mohan, C., Berg, L.J., et al. Suppression of systemic autoimmunity by the innate immune adaptor STING. Proc Natl Acad Sci U S A 112 (2015), E710–E717 This paper uses lpr model of murine systemic autoimmunity to provide evidence that STING suppresses the TLR-induced innate signaling in systemic lupus erythematosus (SLE). Mechanistically, STING-deficient macrophages failed to express negative regulators of immune activation and thus were hyperresponsive to TLR ligands. These data describe STING as a key natural regulator of SLE, which can be manipulated to provide disease-specific therapeutics.
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Sharma, S.1
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Huyler, A.H.7
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Berg, L.J.10
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9
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Self-DNA, STING-dependent signaling and the origins of autoinflammatory disease
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9 Ahn, J., Barber, G.N., Self-DNA, STING-dependent signaling and the origins of autoinflammatory disease. Curr Opin Immunol 31 (2014), 121–126.
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Ahn, J.1
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Activated STING in a vascular and pulmonary syndrome
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Using whole exome sequencing, the authors analyzed the DNA of a patient(s) with early-onset auto-inflammatory disease to identify TMEM173, encoding STING, as the gene conferring the phenotype. Specifically, three de novo STING mutations confer gain of functions and constitutive activation of STING and hypersensitivity to ligand stimulation. In addition to being clinically relevant, this work reveals spontaneous activation of STING via the DD (dimerization domain) thus providing important mechanistic insight on STING-activation.
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10•• Liu, Y., Jesus, A.A., Marrero, B., Yang, D., Ramsey, S.E., Montealegre Sanchez, G.A., Tenbrock, K., Wittkowski, H., Jones, O.Y., Kuehn, H.S., et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med 371 (2014), 507–518 Using whole exome sequencing, the authors analyzed the DNA of a patient(s) with early-onset auto-inflammatory disease to identify TMEM173, encoding STING, as the gene conferring the phenotype. Specifically, three de novo STING mutations confer gain of functions and constitutive activation of STING and hypersensitivity to ligand stimulation. In addition to being clinically relevant, this work reveals spontaneous activation of STING via the DD (dimerization domain) thus providing important mechanistic insight on STING-activation.
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N Engl J Med
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Liu, Y.1
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Tenbrock, K.7
Wittkowski, H.8
Jones, O.Y.9
Kuehn, H.S.10
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11
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STING-associated vasculopathy with onset in infancy — a new interferonopathy
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11 Crow, Y.J., Casanova, J.L., STING-associated vasculopathy with onset in infancy — a new interferonopathy. N Engl J Med 371 (2014), 568–571.
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Crow, Y.J.1
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12
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Diverse roles of STING-dependent signaling on the development of cancer
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12 Ahn, J., Konno, H., Barber, G.N., Diverse roles of STING-dependent signaling on the development of cancer. Oncogene, 2015.
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Oncogene
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Ahn, J.1
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13
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Backbone resonance assignments of the 54 kDa dimeric C-terminal domain of murine STING in complex with DMXAA
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13 Lou, Y.C., Kao, Y.F., Chin, K.H., Chen, J.K., Tu, J.L., Chen, C., Chou, S.H., Backbone resonance assignments of the 54 kDa dimeric C-terminal domain of murine STING in complex with DMXAA. Biomol NMR Assign 9 (2015), 271–274.
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Lou, Y.C.1
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14 Crow, Y.J., Type I interferonopathies: mendelian type I interferon up-regulation. Curr Opin Immunol 32 (2015), 7–12.
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Crow, Y.J.1
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15
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Cutting edge: novel Tmem173 allele reveals importance of STING N terminus in trafficking and type I IFN production
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15 Surpris, G., Chan, J., Thompson, M., Ilyukha, V., Liu, B.C., Atianand, M., Sharma, S., Volkova, T., Smirnova, I., Fitzgerald, K.A., et al. Cutting edge: novel Tmem173 allele reveals importance of STING N terminus in trafficking and type I IFN production. J Immunol 196 (2015), 547–552.
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Surpris, G.1
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Sharma, S.7
Volkova, T.8
Smirnova, I.9
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16
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Mitochondrial DNA sensing by STING signaling participates in inflammation, cancer and beyond
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16 Liu, S., Feng, M., Guan, W., Mitochondrial DNA sensing by STING signaling participates in inflammation, cancer and beyond. Int J Cancer 139 (2016), 736–741.
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Liu, S.1
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17
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Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production
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17 White, M.J., McArthur, K., Metcalf, D., Lane, R.M., Cambier, J.C., Herold, M.J., van Delft, M.F., Bedoui, S., Lessene, G., Ritchie, M.E., et al. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell 159 (2014), 1549–1562.
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White, M.J.1
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van Delft, M.F.7
Bedoui, S.8
Lessene, G.9
Ritchie, M.E.10
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18
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84950247027
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Limiting cholesterol biosynthetic flux spontaneously engages type I IFN signaling
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18 York, A.G., Williams, K.J., Argus, J.P., Zhou, Q.D., Brar, G., Vergnes, L., Gray, E.E., Zhen, A., Wu, N.C., Yamada, D.H., et al. Limiting cholesterol biosynthetic flux spontaneously engages type I IFN signaling. Cell 163 (2015), 1716–1729.
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York, A.G.1
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Gray, E.E.7
Zhen, A.8
Wu, N.C.9
Yamada, D.H.10
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19
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Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA
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19 Rongvaux, A., Jackson, R., Harman, C.C., Li, T., West, A.P., de Zoete, M.R., Wu, Y., Yordy, B., Lakhani, S.A., Kuan, C.Y., et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell 159 (2014), 1563–1577.
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Rongvaux, A.1
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Wu, Y.7
Yordy, B.8
Lakhani, S.A.9
Kuan, C.Y.10
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20
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84928537166
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Mitochondrial DNA stress primes the antiviral innate immune response
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The authors of this paper report that mitochondrial stress is induced in response to the infection. The leaking mitochondrial DNA activates the innate immune response via cGAS-STING pathway. Thus, stressed mitochondria can be viewed as a sensor of infection.
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20• West, A.P., Khoury-Hanold, W., Staron, M., Tal, M.C., Pineda, C.M., Lang, S.M., Bestwick, M., Duguay, B.A., Raimundo, N., MacDuff, D.A., et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520 (2015), 553–557 The authors of this paper report that mitochondrial stress is induced in response to the infection. The leaking mitochondrial DNA activates the innate immune response via cGAS-STING pathway. Thus, stressed mitochondria can be viewed as a sensor of infection.
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Nature
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West, A.P.1
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Tal, M.C.4
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Bestwick, M.7
Duguay, B.A.8
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MacDuff, D.A.10
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21
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UV light potentiates STING (stimulator of interferon genes)-dependent innate immune signaling through deregulation of ULK1 (Unc51-like kinase 1)
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21 Kemp, M.G., Lindsey-Boltz, L.A., Sancar, A., UV light potentiates STING (stimulator of interferon genes)-dependent innate immune signaling through deregulation of ULK1 (Unc51-like kinase 1). J Biol Chem 290 (2015), 12184–12194.
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Kemp, M.G.1
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22
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Sequential activation of two pathogen-sensing pathways required for type I interferon expression and resistance to an acute DNA virus infection
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22 Xu, R.H., Wong, E.B., Rubio, D., Roscoe, F., Ma, X., Nair, S., Remakus, S., Schwendener, R., John, S., Shlomchik, M., et al. Sequential activation of two pathogen-sensing pathways required for type I interferon expression and resistance to an acute DNA virus infection. Immunity 43 (2015), 1148–1159.
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Xu, R.H.1
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23
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84938805575
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Herpesvirus genome recognition induced acetylation of nuclear IFI16 is essential for its cytoplasmic translocation, inflammasome and IFN-beta responses
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23 Ansari, M.A., Dutta, S., Veettil, M.V., Dutta, D., Iqbal, J., Kumar, B., Roy, A., Chikoti, L., Singh, V.V., Chandran, B., Herpesvirus genome recognition induced acetylation of nuclear IFI16 is essential for its cytoplasmic translocation, inflammasome and IFN-beta responses. PLoS Pathog, 11, 2015, e1005019.
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Ansari, M.A.1
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24
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84936748794
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BRCA1 regulates IFI16 mediated nuclear innate sensing of herpes viral DNA and subsequent induction of the innate inflammasome and interferon-beta responses
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24 Dutta, D., Dutta, S., Veettil, M.V., Roy, A., Ansari, M.A., Iqbal, J., Chikoti, L., Kumar, B., Johnson, K.E., Chandran, B., BRCA1 regulates IFI16 mediated nuclear innate sensing of herpes viral DNA and subsequent induction of the innate inflammasome and interferon-beta responses. PLoS Pathog, 11, 2015, e1005030.
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25
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Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING
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25 Holm, C.K., Jensen, S.B., Jakobsen, M.R., Cheshenko, N., Horan, K.A., Moeller, H.B., Gonzalez-Dosal, R., Rasmussen, S.B., Christensen, M.H., Yarovinsky, T.O., et al. Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nat Immunol 13 (2012), 737–743.
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Holm, C.K.1
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Yarovinsky, T.O.10
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26
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84959036465
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Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses
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At the mechanistic level, this study identifies a fusion peptide in the N-terminal domain of the hemagglutinin of the dsRNA influenza virus which interacts with the dimerization domain of STING thus preventing the dimerization of STING and downstream IFN production. At the conceptual level, the data allude to existence of another pathway that is STING-dependent but cGAS-independent that interferes with the cellular membrane and provides ligand-independent activation of STING.
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26•• Holm, C.K., Rahbek, S.H., Gad, H.H., Bak, R.O., Jakobsen, M.R., Jiang, Z., Hansen, A.L., Jensen, S.K., Sun, C., Thomsen, M.K., et al. Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses. Nat Commun, 7, 2016, 10680 At the mechanistic level, this study identifies a fusion peptide in the N-terminal domain of the hemagglutinin of the dsRNA influenza virus which interacts with the dimerization domain of STING thus preventing the dimerization of STING and downstream IFN production. At the conceptual level, the data allude to existence of another pathway that is STING-dependent but cGAS-independent that interferes with the cellular membrane and provides ligand-independent activation of STING.
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Nat Commun
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Holm, C.K.1
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27
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84961187349
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2+ signalling and incoming genome sensing are required for the host response to low-level enveloped virus particle entry
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2+ signaling sensitizes cells to recognize genomes within incoming virus particles. Altogether, this work further supports the second signal caused by viruses and change the cellular environment, and oxidative stress or endoplasmic reticulum stress that amplify antiviral signaling.
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2+ signaling sensitizes cells to recognize genomes within incoming virus particles. Altogether, this work further supports the second signal caused by viruses and change the cellular environment, and oxidative stress or endoplasmic reticulum stress that amplify antiviral signaling.
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29 Tsuchida, T., Zou, J., Saitoh, T., Kumar, H., Abe, T., Matsuura, Y., Kawai, T., Akira, S., The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity 33 (2010), 765–776.
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30 Chen, H., Sun, H., You, F., Sun, W., Zhou, X., Chen, L., Yang, J., Wang, Y., Tang, H., Guan, Y., et al. Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 147 (2011), 436–446.
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31 Seo, G.J., Yang, A., Tan, B., Kim, S., Liang, Q., Choi, Y., Yuan, W., Feng, P., Park, H.S., Jung, J.U., Akt kinase-mediated checkpoint of cGAS DNA sensing pathway. Cell Rep 13 (2015), 440–449.
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32 Alexander, M., Hu, R., Runtsch, M.C., Kagele, D.A., Mosbruger, T.L., Tolmachova, T., Seabra, M.C., Round, J.L., Ward, D.M., O'Connell, R.M., Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat Commun, 6, 2015, 7321.
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Bruton's tyrosine kinase phosphorylates DDX41 and activates its binding of dsDNA and STING to initiate type 1 interferon response
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33 Lee, K.G., Kim, S.S., Kui, L., Voon, D.C., Mauduit, M., Bist, P., Bi, X., Pereira, N.A., Liu, C., Sukumaran, B., et al. Bruton's tyrosine kinase phosphorylates DDX41 and activates its binding of dsDNA and STING to initiate type 1 interferon response. Cell Rep 10 (2015), 1055–1065.
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