Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF-κB Activation through TBK1

Abe, Takayuki; Barber, Glen N.

doi:10.1128/jvi.00037-14

Cited by 771interferon and immune responsesNF-κB Signaling PathwaysImmune Response and Inflammation

Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF-κB Activation through TBK1

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Abe, Takayuki, Barber, Glen N.·2014·Journal of Virology

DOI 10.1128/jvi.00037-14PMC PMC4019140

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Abstract

STING (stimulator of interferon genes) is known to control the induction of innate immune genes in response to the recognition of cytosolic DNA species, including the genomes of viruses such as herpes simplex virus 1 (HSV-1). However, while STING is essential for protection of the host against numerous DNA pathogens, sustained STING activity can lead to lethal inflammatory disease. It is known that STING utilizes interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) pathways to exert its effects, although the signal transduction mechanisms remain to be clarified fully. Here we demonstrate that in addition to the activation of these pathways, potent induction of the Jun N-terminal protein kinase/stress-activated protein kinase (JNK/SAPK) pathway was similarly observed in response to STING activation by double-stranded DNA (dsDNA). Furthermore, TANK-binding kinase 1 (TBK1) associated with STING was found to facilitate dsDNA-mediated canonical activation of NF-κB as well as IRF3 to promote proinflammatory gene transcription. The triggering of NF-κB function was noted to require TRAF6 activation. Our findings detail a novel dsDNA-mediated NF-κB activation pathway facilitated through a STING-TRAF6-TBK1 axis and suggest a target for therapeutic intervention to plausibly stimulate antiviral activity or, alternatively, avert dsDNA-mediated inflammatory disease. IMPORTANCE The IKK complex, which is composed of two catalytic subunits, IKKα and IKKβ, has been suggested to be essential for the activation of canonical NF-κB signaling in response to various stimuli, including cytokines (e.g., interleukin-1α [IL-1α] and tumor necrosis factor alpha [TNF-α]), Toll-like receptor (TLR) ligands (e.g., lipopolysaccharide [LPS]), and dsRNAs derived from viruses, or a synthetic analog. STING has been identified as a critical signaling molecule required for the detection of cytosolic dsDNAs derived from pathogens and viruses. However, little is known about how cytosolic dsDNA triggers NF-κB signaling. In the present study, we demonstrate that TBK1, identified as an IKK-related kinase, may predominantly control the activation of NF-κB in response to dsDNA signaling via STING through the IKKαβ activation loop. Thus, our results establish TBK1 as a downstream kinase controlling dsDNA-mediated IRF3 and NF-κB signaling dependent on STING.

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STING also increases IFN-I by activating the NF-κB pathway.
“Besides, STING also increases IFN-I by activating NF-κB pathway [260].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [260]

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Sun, L., Wu, J., Du, F., Chen, X., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1232458 · Cited by 4,996 · see citing works
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Wu, J., Sun, L., Chen, X., Du, F., Shi, H., Chen, C., & Chen, Z. J. (2012) · Science · doi:10.1126/science.1229963 · Cited by 2,574 · see citing works
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Burdette, D. L., Monroe, K. M., Sotelo-Troha, K., Iwig, J. S., Eckert, B., Hyodo, M., Hayakawa, Y., & Vance, R. E. (2011) · Nature · doi:10.1038/nature10429 · Cited by 1,570 · see citing works
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Zhong, B., Yang, Y., Li, S., Wang, Y., Li, Y., Diao, F., Lei, C., He, X., Zhang, L., Tien, P., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.09.003 · Cited by 1,513 · see citing works
Requirement for glycogen synthase kinase-3β in cell survival and NF-κB activation
Hoeflich, K. P., Luo, J., Rubie, E. A., Tsao, M., Jin, O., & Woodgett, J. R. (2000) · Nature · doi:10.1038/35017574 · Cited by 1,394 · see citing works
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Tanaka, Y., & Chen, Z. J. (2012) · Science Signaling · doi:10.1126/scisignal.2002521 · Cited by 1,314 · see citing works
Shaping the nuclear action of NF-κB
Chen, L., & Greene, W. C. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1368 · Cited by 1,219 · see citing works
RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway
Chiu, Y., MacMillan, J. B., & Chen, Z. J. (2009) · Cell · doi:10.1016/j.cell.2009.06.015 · Cited by 1,185 · see citing works
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Stetson, D. B., & Medzhitov, R. M. (2006) · Immunity · doi:10.1016/j.immuni.2005.12.003 · Cited by 1,003 · see citing works
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Nagata, S., Hanayama, R., & Kawane, K. (2010) · Cell · doi:10.1016/j.cell.2010.02.014 · Cited by 877 · see citing works
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Sun, W., Li, Y., Chen, L., Chen, H., You, F., Zhou, X., Zhou, Y., Zhai, Z., Chen, D., & Jiang, Z. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900850106 · Cited by 862 · see citing works
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Saitoh, T., Fujita, N., Hayashi, T., Takahara, K., Satoh, T., Lee, H., Matsunaga, K., Kageyama, S., Omori, H., Noda, T., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911267106 · Cited by 854 · see citing works
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Madrid, L. V., Mayo, M. W., Reuther, J. Y., & Baldwin, A. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101103200 · Cited by 777 · see citing works
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Paludan, S. R., & Bowie, A. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.004 · Cited by 764 · see citing works
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Konno, H., Konno, K., & Barber, G. N. (2013) · Cell · doi:10.1016/j.cell.2013.09.049 · Cited by 676 · see citing works
Self-citation
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Pomerantz, J. L., & Baltimore, D. (1999) · The EMBO Journal · doi:10.1093/emboj/18.23.6694 · Cited by 595 · see citing works
The Roles of Two IκB Kinase-related Kinases in Lipopolysaccharide and Double Stranded RNA Signaling and Viral Infection
Hemmi, H., Takeuchi, O., Sato, S., Yamamoto, M., Kaisho, T., Sanjo, H., Kawai, T., Hoshino, K., Takeda, K., & Akira, S. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040520 · Cited by 576 · see citing works
STING manifests self DNA-dependent inflammatory disease
Ahn, J., Gutman, D. M., Saijo, S., & Barber, G. N. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215006109 · Cited by 512 · see citing works
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Tsuchida, T., Zou, J. P., Saitoh, T., Kumar, H., Abe, T., Matsuura, Y., Kawai, T., & Akira, S. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.013 · Cited by 488 · see citing works
Self-citation
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Zhong, B., Zhang, L., Lei, C., Li, Y., Mao, A., Yang, Y. F., Wang, Y., Zhang, X., & Shu, H. (2009) · Immunity · doi:10.1016/j.immuni.2009.01.008 · Cited by 478 · see citing works
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Häcker, H., Tseng, P.-H., & Karin, M. (2011) · Nature Reviews Immunology · doi:10.1038/nri2998 · Cited by 471 · see citing works
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Jin, L., Waterman, P. M., Jonscher, K. R., Short, C. M., Reisdorph, N. A., & Cambier, J. C. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00640-08 · Cited by 451 · see citing works
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Conlon, J. E., Burdette, D. L., Sharma, S., Bhat, N., Thompson, M., Jiang, Z., Rathinam, V. A. K., Monks, B. G., Jin, T., Xiao, T. S., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300097 · Cited by 441 · see citing works
Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif
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Perry, A. K., Chow, E. K., Goodnough, J. B., Yeh, W., & Cheng, G. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040528 · Cited by 399 · see citing works
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Zhang, J., Hu, M., Wang, Y., & Shu, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.362608 · Cited by 390 · see citing works
Deficiency of T2K leads to apoptotic liver degeneration and impaired NF‐κB‐dependent gene transcription
Bonnard, M., Mirtsos, C., Suzuki, S., Graham, K., Huang, J., Ng, M., Itié, A., Wakeham, A., Shahinian, A., Henzel, W. J., et al. (2000) · The EMBO Journal · doi:10.1093/emboj/19.18.4976 · Cited by 381 · see citing works
NAK is an IκB kinase-activating kinase
Tojima, Y., Fujimoto, A., Delhase, M., Chen, Y., Hatakeyama, S., Nakayama, K. I., Kaneko, Y. S., Nimura, Y., Motoyama, N., Ikeda, K., et al. (2000) · Nature · doi:10.1038/35008109 · Cited by 375 · see citing works
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Self-citation
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Self-citation
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Prantner, D., Perkins, D. J., Lai, W., Williams, M. S., Sharma, S., Fitzgerald, K. A., & Vogel, S. N. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.382986 · Cited by 220 · see citing works
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Zarnegar, B. J., Yamazaki, S., He, J. Q., & Cheng, G. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707959105 · Cited by 183 · see citing works
The chemotherapeutic agent DMXAA potently and specifically activates the TBK1–IRF-3 signaling axis
Roberts, Z. J., Goutagny, N., Perera, P., Kato, H., Kumar, H., Kawai, T., Akira, S., Savan, R., Echo, D. V., Fitzgerald, K. A., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20061845 · Cited by 167 · see citing works
Rescue of TRAF3-null mice by p100 NF-κB deficiency
He, J. Q., Zarnegar, B. J., Oganesyan, G., Saha, S. K., Yamazaki, S., Doyle, S. E., Dempsey, P. W., & Cheng, G. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061166 · Cited by 166 · see citing works
Identification of NAP1, a Regulatory Subunit of IκB Kinase-Related Kinases That Potentiates NF-κB Signaling
Fujita, F., Taniguchi, Y., Kato, T., Narita, Y., Furuya, A., Ogawa, T., Sakurai, H., Joh, T., Itoh, M., Delhase, M., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7780-7793.2003 · Cited by 164 · see citing works
A functional C-terminal TRAF3-binding site in MAVS participates in positive and negative regulation of the IFN antiviral response
Paz, S., Vilasco, M., Werden, S. J., Arguello, M., Joseph-Pillai, D., Zhao, T., Nguyên, T. L.-A., Sun, Q., MEURS, E. F., Lin, R., et al. (2011) · Cell Research · doi:10.1038/cr.2011.2 · Cited by 148 · see citing works
Herpes Simplex Virus Immediate-Early ICP0 Protein Inhibits Toll-Like Receptor 2-Dependent Inflammatory Responses and NF-κB Signaling
van Lint, A. L., Murawski, M. R., Goodbody, R., Severa, M., Fitzgerald, K. A., Finberg, R. W., Knipe, D. M., & Kurt‐Jones, E. A. (2010) · Journal of Virology · doi:10.1128/jvi.00063-10 · Cited by 146 · see citing works
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Jin, L., Xu, L., Yang, I. V., Davidson, E. J., Schwartz, D. A., Wurfel, M. M., & Cambier, J. C. (2011) · Genes and Immunity · doi:10.1038/gene.2010.75 · Cited by 130 · see citing works
The interplay between viruses and innate immune signaling: Recent insights and therapeutic opportunities
Unterholzner, L., & Bowie, A. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.07.043 · Cited by 123 · see citing works
TRAF6 Establishes Innate Immune Responses by Activating NF-κB and IRF7 upon Sensing Cytosolic Viral RNA and DNA
Konno, H., Yamamoto, T., Yamazaki, K., Gohda, J., Akiyama, T., Semba, K., Goto, H., Kato, A., Yujiri, T., Imai, T., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005674 · Cited by 122 · see citing works
Efficient Replication by Herpes Simplex Virus Type 1 Involves Activation of the IκB Kinase-IκB-p65 Pathway
Gregory, D. A., Hargett, D., Holmes, D., Money, E. S., & Bachenheimer, S. L. (2004) · Journal of Virology · doi:10.1128/jvi.78.24.13582-13590.2004 · Cited by 117 · see citing works
Type I Interferon in Systemic Lupus Erythematosus
Crow, M. K. (2007) · Springer eBooks · doi:10.1007/978-3-540-71329-6_17 · Cited by 113 · see citing works
TRAF6 and MEKK1 Play a Pivotal Role in the RIG-I-like Helicase Antiviral Pathway
Yoshida, R., Takaesu, G., Yoshida, H., Okamoto, F., Yoshioka, T., Choi, Y., Akira, S., Kawai, T., Yoshimura, A., & Kobayashi, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806576200 · Cited by 107 · see citing works
Cutting Edge: Role of TANK-Binding Kinase 1 and Inducible IκB Kinase in IFN Responses against Viruses in Innate Immune Cells
Matsui, K., Kumagai, Y., Kato, H., Sato, S., Kawagoe, T., Uematsu, S., Takeuchi, O., & Akira, S. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.9.5785 · Cited by 87 · see citing works
Activation of NF-κB in cells productively infected with HSV-1 depends on activated protein kinase R and plays no apparent role in blocking apoptosis
Taddeo, B., Luo, T. R., Zhang, W., & Roizman, B. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2034952100 · Cited by 79 · see citing works
TANK-Binding Kinase-1 Plays an Important Role during In Vitro and In Vivo Type I IFN Responses to DNA Virus Infections
Miyahira, A. K., Shahangian, A., Hwang, S., Sun, R., & Cheng, G. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802466 · Cited by 55 · see citing works
IκB Kinase α Phosphorylation of TRAF4 Downregulates Innate Immune Signaling
Marinis, J. M., Hutti, J. E., Homer, C. R., Cobb, B. A., Cantley, L. C., McDonald, C., & Abbott, D. W. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00106-12 · Cited by 35 · see citing works

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Haag, S. M., Gulen, M. F., Reymond, L., Gibelin, A., Abrami, L., Decout, A., Heymann, M., van der Goot, F. G., Turcatti, G., Behrendt, R., et al. (2018) · Nature · doi:10.1038/s41586-018-0287-8 · Cited by 1,178 · see citing works
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Zierhut, C., Yamaguchi, N., Paredes, M. C. G., Luo, J., Carroll, T., & Funabiki, H. (2019) · Cell · doi:10.1016/j.cell.2019.05.035 · Cited by 403 · see citing works
Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis
Collins, A. C., Cai, H., Li, T., Franco, L. H., Li, X.-D., Nair, V. R., Scharn, C. R., Stamm, C. E., Levine, B., Chen, Z. J., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.05.005 · Cited by 384 · see citing works
DNA damage and repair in age-related inflammation
Zhao, Y., Simon, M. A., Seluanov, A., & Gorbunova, V. A. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00751-y · Cited by 393 · see citing works
Mitochondria-associated membranes (MAMs) and inflammation
Missiroli, S., Patergnani, S., Caroccia, N., Pedriali, G., Perrone, M., Previati, M., Wieckowski, M. R., & Giorgi, C. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0027-2 · Cited by 389 · see citing works
Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways
Zevini, A., Olagnier, D. P., & Hiscott, J. B. (2017) · Trends in Immunology · doi:10.1016/j.it.2016.12.004 · Cited by 364 · see citing works
Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy
Garland, K. M., Sheehy, T. L., & Wilson, J. T. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00750 · Cited by 368 · see citing works
Cutting Edge: Activation of STING in T Cells Induces Type I IFN Responses and Cell Death
Larkin, B., Ilyukha, V., Sorokin, M., Buzdin, A., Vannier, E., & Poltorak, A. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601999 · Cited by 361 · see citing works
The cGAS–STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy
Oduro, P. K., Zheng, X., Wei, J., Yang, Y., Wang, Y., Zhang, H., Liu, E., Gao, X., Du, M., & Wang, Q. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.05.011 · Cited by 349 · see citing works
STING pathway agonism as a cancer therapeutic
Flood, B. A., Higgs, E. F., Li, S., Luke, J. J., & Gajewski, T. F. (2019) · Immunological Reviews · doi:10.1111/imr.12765 · Cited by 338 · see citing works
New insights into the evasion of host innate immunity by Mycobacterium tuberculosis
Chai, Q., Wang, L., Liu, C. H., & Ge, B. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0502-z · Cited by 336 · see citing works
Trafficking-Mediated STING Degradation Requires Sorting to Acidified Endolysosomes and Can Be Targeted to Enhance Anti-tumor Response
Gonugunta, V. K., Sakai, T., Pokatayev, V., Yang, K., Wu, J., Dobbs, N., & Yan, N. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.061 · Cited by 326 · see citing works
Manganese salts function as potent adjuvants
Zhang, R., Wang, C., Guan, Y., Wei, X., Sha, M., Yi, M., Jing, M., Lv, M., Guo, W., Xu, J., et al. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00669-w · Cited by 321 · see citing works
Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis
Li, J., Duran, M. A., Dhanota, N., Chatila, W. K., Bettigole, S. E., Kwon, J., Sriram, R. K., Humphries, M. P., Salto-Tellez, M., James, J. A., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0387 · Cited by 312 · see citing works
Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes
Cerboni, S., Jeremiah, N., Gentili, M., Gehrmann, U., Conrad, C., Stolzenberg, M., Pïcard, C., Neven, B., Fischer, A., Amigorena, S., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20161674 · Cited by 303 · see citing works
Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression
Lama, L., Adura, C., Xie, W., Tomita, D., Kamei, T., Kuryavyi, V., Gogakos, T., Steinberg, J. I., Miller, M., Ramos-Espiritu, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08620-4 · Cited by 303 · see citing works
Trial watch: STING agonists in cancer therapy
Le Naour, J., Zitvogel, L., Galluzzi, L., Vacchelli, E., & Kroemer, G. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1777624 · Cited by 289 · see citing works
Cytoplasmic DNA: sources, sensing, and role in aging and disease
Miller, K. N., Victorelli, S. G., Salmonowicz, H., Dasgupta, N., Liu, T., Passos, J. F., & Adams, P. D. (2021) · Cell · doi:10.1016/j.cell.2021.09.034 · Cited by 288 · see citing works
STING inhibitors target the cyclic dinucleotide binding pocket
Hong, Z., Mei, J., Li, C., Bai, G., Maimaiti, M., Hu, H., Yu, W., Sun, L., Zhang, L., Cheng, D., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2105465118 · Cited by 291 · see citing works
Evolutionary Origins of cGAS-STING Signaling
Margolis, S. R., Wilson, S. C., & Vance, R. E. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.03.004 · Cited by 273 · see citing works
Structural mechanism of cGAS inhibition by the nucleosome
Pathare, G. R., Decout, A., Glück, S., Cavadini, S., Makasheva, K., Hovius, R., Kempf, G., Weiss, J., Kozicka, Z., Guey, B., et al. (2020) · Nature · doi:10.1038/s41586-020-2750-6 · Cited by 273 · see citing works
Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy
Hou, Y., Liang, H. L., Rao, E., Zheng, W., Huang, X., Deng, L., Zhang, Y., Yu, X., Xu, M. M., Mauceri, H. J., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.07.008 · Cited by 270 · see citing works
Anti-Carcinogenic Glucosinolates in Cruciferous Vegetables and Their Antagonistic Effects on Prevention of Cancers
Soundararajan, P., & Kim, J. S. (2018) · Molecules · doi:10.3390/molecules23112983 · Cited by 268 · see citing works
Chromatin‐bound cGAS is an inhibitor of DNA repair and hence accelerates genome destabilization and cell death
Jiang, H., Xue, X., Panda, S., Kawale, A. S., Hooy, R. M., Liang, F., Sohn, J., Sung, P., & Gekara, N. O. (2019) · The EMBO Journal · doi:10.15252/embj.2019102718 · Cited by 263 · see citing works
Emerging role of STING signalling in CNS injury: inflammation, autophagy, necroptosis, ferroptosis and pyroptosis
Hu, X., Zhang, H., Zhang, Q., Yao, X. X., Ni, W., & Zhou, K. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02602-y · Cited by 256 · see citing works
Cytosolic DNA Sensing in Organismal Tumor Control
Vanpouille-Box, C., Demaria, S., Formenti, S. C., & Galluzzi, L. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.013 · Cited by 250 · see citing works
Mitochondrial function in immune cells in health and disease
Faas, M. M., & de Vos, P. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165845 · Cited by 246 · see citing works
The cGAS-cGAMP-STING Pathway: A Molecular Link Between Immunity and Metabolism
Bai, J., & Liu, F. (2019) · Diabetes · doi:10.2337/dbi18-0052 · Cited by 246 · see citing works
Trial watch: TLR3 agonists in cancer therapy
Le Naour, J., Galluzzi, L., Zitvogel, L., Kroemer, G., & Vacchelli, E. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1771143 · Cited by 239 · see citing works
Activation of the STING-IRF3 pathway promotes hepatocyte inflammation, apoptosis and induces metabolic disorders in nonalcoholic fatty liver disease
Qiao, J. T., Cui, C., Qing, L., Wang, L., He, T., Yan, F., Liu, F. Q., Shen, Y. H., Hou, X., & Chen, L. (2017) · Metabolism · doi:10.1016/j.metabol.2017.09.010 · Cited by 239 · see citing works
STING promotes NLRP3 localization in ER and facilitates NLRP3 deubiquitination to activate the inflammasome upon HSV-1 infection
Wang, W., Hu, D., Feng, Y., Wu, J., Li, A., Wang, Y., Cheng, K., Tian, M., Xiao, F., Zhang, Q., et al. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008335 · Cited by 240 · see citing works
Phosphorylation and chromatin tethering prevent cGAS activation during mitosis
Li, T., Huang, T., Du, M., Chen, X., Du, F., Ren, J., & Chen, Z. J. (2021) · Science · doi:10.1126/science.abc5386 · Cited by 238 · see citing works
The Role of Mitochondria in Inflammation: From Cancer to Neurodegenerative Disorders
Missiroli, S., Genovese, I., Perrone, M., Vezzani, B., Vitto, V. A. M., & Giorgi, C. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9030740 · Cited by 231 · see citing works
The Impact of Radiation-Induced DNA Damage on cGAS-STING-Mediated Immune Responses to Cancer
Storozynsky, Q. T., & Hitt, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228877 · Cited by 233 · see citing works
NEMO–IKKβ Are Essential for IRF3 and NF-κB Activation in the cGAS–STING Pathway
Fang, R., Wang, C., Jiang, Q., Lv, M., Gao, P., Yu, X., Mu, P., Zhang, R., Bi, S., Feng, J., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700699 · Cited by 227 · see citing works
STING Signaling Promotes Inflammation in Experimental Acute Pancreatitis
Zhao, Q., Wei, Y., Pandol, S. J., Li, L., & Habtezion, A. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.01.065 · Cited by 226 · see citing works
Innate immune recognition of DNA: A recent history
Dempsey, A., & Bowie, A. (2015) · Virology · doi:10.1016/j.virol.2015.03.013 · Cited by 216 · see citing works
Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-κB Signaling Adaptation
Mann, C. C. D. O., Orzalli, M. H., King, D., Kagan, J. C., Lee, A. S. Y., & Kranzusch, P. J. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.098 · Cited by 220 · see citing works
The Race between Host Antiviral Innate Immunity and the Immune Evasion Strategies of Herpes Simplex Virus 1
Zhu, H., & Zheng, C. (2020) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00099-20 · Cited by 214 · see citing works
Multifaceted functions of STING in human health and disease: from molecular mechanism to targeted strategy
Zhang, Z., Zhou, H., Ouyang, X., Dong, Y., Sarapultsev, A., Luo, S., & Hu, D. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01252-z · Cited by 216 · see citing works
STING-associated vasculopathy develops independently of IRF3 in mice
Warner, J. D., Irizarry-Caro, R. A., Bennion, B. G., Ai, T. L., Smith, A. M., Miner, C. A., Sakai, T., Gonugunta, V. K., Wu, J., Platt, D. J., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20171351 · Cited by 204 · see citing works
Lipotoxicity-induced mtDNA release promotes diabetic cardiomyopathy by activating the cGAS-STING pathway in obesity-related diabetes
Ma, X. M., Geng, K., Law, B. Y. K., Wang, P., Pu, Y. L., Chen, Q., Xu, H. W., Tan, X. Z., Jiang, Z. Z., & Xu, Y. (2022) · Cell Biology and Toxicology · doi:10.1007/s10565-021-09692-z · Cited by 208 · see citing works
Role of the cGAS–STING pathway in cancer development and oncotherapeutic approaches
Khoo, L. T., & Chen, L. (2018) · The EMBO Reports · doi:10.15252/embr.201846935 · Cited by 204 · see citing works
Liposomes loaded with a STING pathway ligand, cyclic di-GMP, enhance cancer immunotherapy against metastatic melanoma
Nakamura, T., Miyabe, H., Hyodo, M., Sato, Y., Hayakawa, Y., & Harashima, H. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.026 · Cited by 198 · see citing works
NF-κB activation enhances STING signaling by altering microtubule-mediated STING trafficking
Zhang, L., Wei, X., Wang, Z., Liu, P., Hou, Y., Xu, Y., Su, H., Koci, M. D., Yin, H., & Zhang, C. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112185 · Cited by 194 · see citing works
Cellular Innate Immunity: An Old Game with New Players
Gasteiger, G., D’Osualdo, A., Schubert, D. A., Weber, A. N. R., Bruscia, E. M., & Hartl, D. (2016) · Journal of Innate Immunity · doi:10.1159/000453397 · Cited by 191 · see citing works
The cGAS/STING Pathway: A Novel Target for Cancer Therapy
Gan, Y., Li, X., Han, S., Liang, Q., Ma, X., Rong, P., Wang, W., & Li, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.795401 · Cited by 190 · see citing works
DNA-stimulated cell death: implications for host defence, inflammatory diseases and cancer
Paludan, S. R., Reinert, L. S., & Hornung, V. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-018-0117-0 · Cited by 183 · see citing works
Promising Targets for Cancer Immunotherapy: TLRs, RLRs, and STING-Mediated Innate Immune Pathways
Li, K., Qu, S., Chen, X., Wu, Q., & Shi, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020404 · Cited by 182 · see citing works
mtDNA-STING Axis Mediates Microglial Polarization via IRF3/NF-κB Signaling After Ischemic Stroke
Kong, L., Li, W., Chang, E., Wang, W., Shen, N., Xu, X., Wang, X., Zhang, Y., Sun, W., Hu, W., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.860977 · Cited by 178 · see citing works
RAD51 interconnects between DNA replication, DNA repair and immunity
Bhattacharya, S., Kalayarasan, S., Abdisalaam, S., Su, F., Raj, P., Dozmorov, I. M., Mishra, R., Wakeland, E. K., Ghose, S., Mukherjee, S., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx126 · Cited by 176 · see citing works
IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway
Cai, H., Yan, L., Liu, N., Xu, M. M., & Cai, H. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109790 · Cited by 175 · see citing works
An updated molecular basis for mussel immunity
Gerdol, M., & Venier, P. (2015) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2015.02.013 · Cited by 171 · see citing works
KDM5 histone demethylases repress immune response via suppression of STING
Wu, L., Cao, J. P., Cai, W. L., Lang, S. M., Horton, J. R., Jansen, D. J., Liu, Z. Z., Chen, J. F.-Y., Zhang, M., Mott, B. T., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2006134 · Cited by 175 · see citing works
Evasion of host antiviral innate immunity by HSV-1, an update
Su, C., Zhan, G., & Zheng, C. (2016) · Virology Journal · doi:10.1186/s12985-016-0495-5 · Cited by 175 · see citing works
Genomic instability, inflammatory signaling and response to cancer immunotherapy
Chen, M., Linstra, R., & van Vugt, M. A. T. M. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188661 · Cited by 166 · see citing works
Targeting STING to promote antitumor immunity
Chin, E. N., Sulpizio, A., & Lairson, L. L. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.06.010 · Cited by 165 · see citing works
Targeting Stimulator of Interferon Genes (STING): A Medicinal Chemistry Perspective
Zhang, H., You, Q., & Xu, X. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01039 · Cited by 152 · see citing works
Dysbiosis exacerbates colitis by promoting ubiquitination and accumulation of the innate immune adaptor STING in myeloid cells
Shmuel-Galia, L., Humphries, F., Lei, X., Ceglia, S., Wilson, R., Jiang, Z., Ketelut-Carneiro, N., Foley, S. E., Pechhold, S. B., Houghton, J., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.05.008 · Cited by 150 · see citing works
Mitochondrial DNA stress signalling protects the nuclear genome
Wu, Z., Oeck, S., West, A. P., Mangalhara, K. C., Sainz, A. G., Newman, L. E., Zhang, X.-O., Wu, L., Yan, Q., Bosenberg, M., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0150-8 · Cited by 146 · see citing works
Regulation of the cGAS-STING Pathway
Zhang, B., Xu, P., & Ablasser, A. (2025) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101721-032910 · Cited by 153 · see citing works
Prospects for combining immune checkpoint blockade with PARP inhibition
Li, A., Yi, M., Qin, S., Chu, Q., Luo, S., & Wu, K. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0784-8 · Cited by 143 · see citing works
“Besides, STING could activate NF-κB pathway which cooperates with IRF3 to upregulate the generation of type I IFN [101].”
Background
Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING
Bruand, M., Barras, D., Mina, M., Ghisoni, E., Morotti, M., Lanitis, E., Fahr, N., Desbuisson, M., Grimm, A. J., Zhang, H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109412 · Cited by 141 · see citing works
The cGAS‐STING pathway: The role of self‐DNA sensing in inflammatory lung disease
Ma, R., Serrano, T. P. O., Davis, J., Prigge, A. D., & Ridge, K. M. (2020) · The FASEB Journal · doi:10.1096/fj.202001607r · Cited by 133 · see citing works
Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease
Welch, G., & Tsai, L. (2022) · The EMBO Reports · doi:10.15252/embr.202154217 · Cited by 129 · see citing works
STING-associated lung disease in mice relies on T cells but not type I interferon
Luksch, H., Stinson, W. A., Platt, D. J., Qian, W., Kalugotla, G., Miner, C. A., Bennion, B. G., Gerbaulet, A., Rösen‐Wolff, A., & Miner, J. J. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.01.044 · Cited by 124 · see citing works
Dance with the Devil: Stress Granules and Signaling in Antiviral Responses
Eiermann, N., Haneke, K., Sun, Z., Stoecklin, G., & Ruggieri, A. (2020) · Viruses · doi:10.3390/v12090984 · Cited by 125 · see citing works
Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases
Pan, J., 宁波大学农产品质量安全危害因子与风险防控国家重点实验室, 浙. 宁. 3., Fei, C.-J., Hu, Y., Wu, X., Nie, L., Chen, J., 宁波大学梅山校区海洋学院生物化学与分子生物学实验室, 浙. 宁. 3., & 浙江省海洋生物工程重点实验室, 浙. 宁. 3. (2023) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2022.464 · Cited by 129 · see citing works
The volume-regulated anion channel LRRC8C suppresses T cell function by regulating cyclic dinucleotide transport and STING–p53 signaling
Concepcion, A. R., Wagner, L. E., Zhu, J., Tao, A. Y., Yang, J. J. J., Khodadadi‐Jamayran, A., Wang, Y., Liu, M., Rose, R. E., Jones, R., et al. (2022) · Nature Immunology · doi:10.1038/s41590-021-01105-x · Cited by 127 · see citing works
Interferon γ-inducible Protein (IFI) 16 Transcriptionally Regulates Type I Interferons and Other Interferon-stimulated Genes and Controls the Interferon Response to both DNA and RNA Viruses
Thompson, M., Sharma, S., Atianand, M., Jensen, S. B., Carpenter, S. B., Knipe, D. M., Fitzgerald, K. A., & Kurt‐Jones, E. A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.554147 · Cited by 126 · see citing works
Activation and Regulation of DNA-Driven Immune Responses
Paludan, S. R. (2015) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00061-14 · Cited by 122 · see citing works
Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies
Iurescia, S., Fioretti, D. P., & Rinaldi, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00711 · Cited by 123 · see citing works
Chromosomal instability as a driver of cancer progression
Chen, X., Agustinus, A. S., Li, J., Bona, M. D., & Bakhoum, S. F. W. (2024) · Nature Reviews Genetics · doi:10.1038/s41576-024-00761-7 · Cited by 134 · see citing works
Inhibition of cGAS-STING-TBK1 signaling pathway by DP96R of ASFV China 2018/1
Wang, X., Wu, J., Wu, Y., Chen, H., Zhang, S., Li, J., Xin, T., Jia, H., Hou, S., Jiang, Y., et al. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.10.103 · Cited by 124 · see citing works
Replication Stress, DNA Damage, Inflammatory Cytokines and Innate Immune Response
Ragu, S., Matos-Rodrigues, G. E., & López, B. S. (2020) · Genes · doi:10.3390/genes11040409 · Cited by 123 · see citing works
Biochemistry, Cell Biology, and Pathophysiology of the Innate Immune cGAS–cGAMP–STING Pathway
Ritchie, C., Carozza, J. A., & Li, L. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-040320-101629 · Cited by 121 · see citing works
The role of cGAS-STING signalling in liver diseases
Chen, R., Du, J., Zhu, H., & Ling, Q. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100324 · Cited by 124 · see citing works
Novel CRBN-Recruiting Proteolysis-Targeting Chimeras as Degraders of Stimulator of Interferon Genes with In Vivo Anti-Inflammatory Efficacy
Liu, J., Yuan, L., Ruan, Y., Deng, B., Yang, Z., Ren, Y., Li, L., Liu, T., Zhao, H., Mai, R., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01948 · Cited by 117 · see citing works
DNA methyltransferase 3 alpha and TET methylcytosine dioxygenase 2 restrain mitochondrial DNA-mediated interferon signaling in macrophages
Cobo, I., Tanaka, T. N., Mangalhara, K. C., Lana, A. J., Yeang, C., Han, C. Z., Schlachetzki, J. C. M., Challcombe, J., Fixsen, B. R., Sakai, M., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.06.022 · Cited by 115 · see citing works
Human Cytomegalovirus Tegument Protein pp65 (pUL83) Dampens Type I Interferon Production by Inactivating the DNA Sensor cGAS without Affecting STING
Biolatti, M., Dell’Oste, V., Pautasso, S., Gugliesi, F., von Einem, J., Krapp, C., Jakobsen, M. R., Borgogna, C., Gariglio, M., Andrea, M. D., et al. (2017) · Journal of Virology · doi:10.1128/jvi.01774-17 · Cited by 115 · see citing works
Pharmacological Modulation of the STING Pathway for Cancer Immunotherapy
Berger, G., Marloye, M., & Lawler, S. E. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.02.007 · Cited by 116 · see citing works
Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors
Ouyang, P., Wang, L., Wu, J., Tian, Y., Chen, C., Li, D., Yao, Z., Chen, R., Xiang, G., Gong, J., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1344272 · Cited by 118 · see citing works

The IKK complex and TBK1/IKKε are recruited to STING through distinct mechanisms to activate NF-κB signaling
Christensen, A. H., Jurkiewicz, A., Jensen, C. S., Kjøge, K., Luo, W., He, W., Chen, Y., Liu, J., Dalskov, L., Bagger, A. B., et al. (2026) · Science Immunology · doi:10.1126/sciimmunol.aeh5148
The STING in the Tail for Cytosolic DNA–Dependent Activation of IRF3
Bowie, A. G. (2012) · Science Signaling · doi:10.1126/scisignal.2002919 · Cited by 47 · see citing works
TBK1 and IKKε Act Redundantly to Mediate STING-Induced NF-κB Responses in Myeloid Cells
Balka, K. R., Louis, C., Saunders, T. L., Smith, A. M., Calleja, D. J., D’Silva, D. B., Moghaddas, F., Tailler, M., Lawlor, K. E., Zhan, Y., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.056 · Cited by 488 · see citing works
TBK1 and IKK epsilon Act Redundantly to Mediate STING-Induced NF-kappa B Responses in Myeloid Cells
Balka, K. R., Louis, C., Saunders, T. L., Smith, A. M., Calleja, D. J., D’Silva, D. B., Moghaddas, F., Tailler, M., Lawlor, K. E., Zhan, Y., et al. (2020) · Cell Reports · Cited by 12 · see citing works
G STING Negatively Regulates Double-Stranded
Cells, I. B., Dong, G., You, M., Ding, L., Fan, H., Liu, F., Ren, D., & Hou, Y. (2016)

Authors: Abe, T., & Barber, G. N.
Affiliations: University of Miami (US)
ORCID: Abe, Takayuki
Barber, Glen N.
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 2014-05-15
Volume: 88
Issue: 10
Pages: 5328-5341
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.00037-14
PMC: PMC4019140
OpenAlex: W2097750604
Cited by: 767
References: 54
Citations by year: 2026: 78 · 2025: 87 · 2024: 104 · 2023: 87 · 2022: 94 · 2021: 75 · 2020: 69 · 2019: 54 · 2018: 44 · 2017: 33 · 2016: 14 · 2015: 22 · 2014: 6
FWCI: 11.41
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (UO1AI083015, R01AI079336, U01AI083015)
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: STING, TBK1, NF-κB activation, TRAF6, IRF3, SAPK/JNK pathway, innate immunity, herpes simplex virus type 1, inflammatory diseases, antiviral signaling
MeSH terms: STING Protein, Animals, Cell Line, Cytosol, DNA, Membrane Proteins, Signal Transduction, Transcriptional Activation, NF-kappa B, Protein Serine-Threonine Kinases, Mice, Knockout, TNF Receptor-Associated Factor 6, Interferon Regulatory Factor-3, Mice

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Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF-κB Activation through TBK1

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