STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
Open accessAbstract
The cellular innate immune system is essential for recognizing pathogen infection and for establishing effective host defence. But critical molecular determinants responsible for facilitating an appropriate immune response-following infection with DNA and RNA viruses, for example-remain to be identified. Here we report the identification, following expression cloning, of a molecule (STING; stimulator of interferon genes) that appears essential for effective innate immune signalling processes. It comprises five putative transmembrane regions, predominantly resides in the endoplasmic reticulum and is able to activate both NF-kappaB and IRF3 transcription pathways to induce expression of type I interferon (IFN-alpha and IFN-beta ) and exert a potent anti-viral state following expression. In contrast, loss of STING rendered murine embryonic fibroblasts extremely susceptible to negative-stranded virus infection, including vesicular stomatitis virus. Further, STING ablation abrogated the ability of intracellular B-form DNA, as well as members of the herpesvirus family, to induce IFN-beta, but did not significantly affect the Toll-like receptor (TLR) pathway. Yeast two-hybrid and co-immunoprecipitation studies indicated that STING interacts with RIG-I and with SSR2 (also known as TRAPbeta), which is a member of the translocon-associated protein (TRAP) complex required for protein translocation across the endoplasmic reticulum membrane following translation. Ablation by RNA interference of both TRAPbeta and translocon adaptor SEC61beta was subsequently found to inhibit STING's ability to stimulate expression of IFN-beta. Thus, as well as identifying a regulator of innate immune signalling, our results imply a potential role for the translocon in innate signalling pathways activated by select viruses as well as intracellular DNA.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TBK1 activates NF-κB to induce expression of interferon and inflammatory cytokines.
“TBK1 also activates NF‐κB to induce expression of IFN and inflammatory cytokines.65, 66, 67”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [65]
The paper’s Abstract reports that STING activates NF-κB and IRF3 pathways to induce type I interferon. It also reports that STING’s activity requires TBK-1, but links TBK-1 to IRF3 activation; it does not establish that TBK1 activates NF-κB or induces inflammatory cytokines. (LLM, conf=0.84)
Experimental — accuracy not yet measuredcGAMP produced by cGAS activation binds to STING on the ER membrane and leads to translocation of STING from ER to Golgi where it is further modified.
“cGAMP produced by cGAS activation binds to STING which is located on the membrane of endoplasmic reticulum (ER)391 and leads to the translocation of STING from ER to the Golgi where it is further modified.392”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [391]
STING is a major pathway for the detection of immunogenic tumors and initiation of a spontaneous T cell response.
“the stimulator of interferon genes (STING) has been shown to be a major pathway for the detection of immunogenic tumors and initiation of a spontaneous T cell response18–21.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [20]
The paper’s Abstract reports STING-mediated responses to intracellular DNA and pathogens, but does not address detection of immunogenic tumors or initiation of a spontaneous T-cell response. Searches for those terms and for tumor, cancer, and antitumor immunity found no passage supporting the attributed claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredTBK1 associated with STING promotes dsDNA-mediated NF-κB activation and proinflammatory gene transcription.
“TBK1 associated with STING also facilitates dsDNA-mediated activation of NF-κB to promote proinflammatory gene transcription (Abe and Barber, 2014; Ishikawa and Barber, 2008).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Ishikawa and Barber, 2008
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S., & Fujita, T. (2004) · Nature Immunology · doi:10.1038/ni1087 · Cited by 3,935 · see citing works
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888 · see citing works
Seth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005) · Cell · doi:10.1016/j.cell.2005.08.012 · Cited by 3,329 · see citing works
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005) · Nature Immunology · doi:10.1038/ni1243 · Cited by 2,562 · see citing works
5'-Triphosphate RNA Is the Ligand for RIG-I
Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.-K., Schlee, M., et al. (2006) · Science · doi:10.1126/science.1132505 · Cited by 2,474 · see citing works
Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005) · Nature · doi:10.1038/nature04193 · Cited by 2,401 · see citing works
RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates
Pichlmair, A., Schulz, O., Tan, C. P., Näslund, T. I., Liljeström, P., Weber, F., & Reis e Sousa, C. (2006) · Science · doi:10.1126/science.1132998 · Cited by 2,210 · see citing works
VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling
Xu, L., Wang, Y., Han, K.-J., Li, L., Zhai, Z., & Shu, H. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.08.014 · Cited by 1,849 · see citing works
Distinct RIG-I and MDA5 Signaling by RNA Viruses in Innate Immunity
Loo, Y.-M., Fornek, J., Crochet, N., Bajwa, G., Perwitasari, O., Martinez-Sobrido, L., Akira, S., Gill, M. A., García-Sastre, A., Katze, M. G., et al. (2008) · Journal of Virology · doi:10.1128/jvi.01080-07 · Cited by 1,071 · see citing works
Recognition of Cytosolic DNA Activates an IRF3-Dependent Innate Immune Response
Stetson, D. B., & Medzhitov, R. M. (2006) · Immunity · doi:10.1016/j.immuni.2005.12.003 · Cited by 1,003 · see citing works
A Toll-like receptor–independent antiviral response induced by double-stranded B-form DNA
Ishii, K. J., Coban, C., Kato, H., Takahashi, K., Torii, Y., Takeshita, F., Ludwig, H., Sutter, G., Suzuki, K., Hemmi, H., et al. (2005) · Nature Immunology · doi:10.1038/ni1282 · Cited by 771 · see citing works
McWhirter, S. M., Fitzgerald, K. A., Rosains, J., Rowe, D. C., Golenbock, D. T., & Maniatis, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2237236100 · Cited by 540 · see citing works
Correlation between Genetic and Geographic Structure in Europe
Lao, O., Lu, T. T., Nothnagel, M., Junge, O., Freitag-Wolf, S., Caliebe, A., Balascakova, M., Bertranpetit, J., Bindoff, L. A., Comas, D., et al. (2008) · Current Biology · doi:10.1016/j.cub.2008.07.049 · Cited by 503 · see citing works
Nonself RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses
Takahasi, K., Yoneyama, M., Nishihori, T., Hirai, R., Kumeta, H., Narita, R., Gale, M., Inagaki, F., & Fujita, T. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.11.028 · Cited by 474 · see citing works
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
Chien, Y., Kim, S., Bumeister, R., Loo, Y., Kwon, S. W., Johnson, C., Balakireva, M. G., Roméo, Y., Kopelovich, L., Gale, M., et al. (2006) · Cell · doi:10.1016/j.cell.2006.08.034 · Cited by 367 · see citing works
Recognition of viruses by innate immunity
Takeuchi, O., & Akira, S. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00562.x · Cited by 341 · see citing works
A FADD-dependent innate immune mechanism in mammalian cells
Balachandran, S., Thomas, E., & Barber, G. N. (2004) · Nature · doi:10.1038/nature03124 · Cited by 294 · see citing works
Self-citationNelson, M. R., Bryc, K., King, K. S., Indap, A., Boyko, A. R., Novembre, J., Briley, L. P., Maruyama, Y., Waterworth, D. M., Waeber, G., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.08.005 · Cited by 293 · see citing works
VSV Disrupts the Rae1/mrnp41 mRNA Nuclear Export Pathway
Waziry, P. A. F., Chakraborty, P., Levay, A. K., Barber, G. N., Ezelle, H. J., Enninga, J., Arana, C., van Deursen, J., & Fontoura, B. M. A. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.11.023 · Cited by 235 · see citing works
Self-citationGenetic analysis of resistance to viral infection
Beutler, B., Eidenschenk, C., Crozat, K., Imler, J., Takeuchi, O., Hoffmann, J. A., & Akira, S. (2007) · Nature reviews. Immunology · doi:10.1038/nri2174 · Cited by 190 · see citing works
A tetrameric complex of membrane proteins in the endoplasmic reticulum
Hartmann, E., Görlich, D., Kostka, S., Otto, A., Kraft, R., Knespel, S., BÜRGER, E., Rapoport, T. A., & Prehn, S. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb17933.x · Cited by 162 · see citing works
Kopp, E. B. (2004) · Medical Entomology and Zoology · Cited by 160 · see citing works
Architecture of the Ribosome–Channel Complex Derived from Native Membranes
Ménétret, J., Hegde, R. S., Heinrich, S. U., Chandramouli, P., Ludtke, S. J., Rapoport, T. A., & Akey, C. W. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.02.053 · Cited by 138 · see citing works
Lipschutz, J. H., Lingappa, V. R., & Mostov, K. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213210200 · Cited by 99 · see citing works
Balachandran, S., Venkataraman, T., Fisher, P. B., & Barber, G. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.4.2429 · Cited by 60 · see citing works
Self-citationRegulation of Antiviral Innate Immune Responses by RIG-I Family of RNA Helicases
Onomoto, K., Yoneyama, M., & Fujita, T. (2007) · Springer eBooks · doi:10.1007/978-3-540-71329-6_10 · Cited by 52 · see citing works
The exocyst meets the translocon: a regulatory circuit for secretion and protein synthesis?
Guo, W., & Novick, P. (2004) · Trends in Cell Biology · doi:10.1016/j.tcb.2003.12.008 · Cited by 40 · see citing works
Mavinakere, M. S., Williamson, C. D., Goldmacher, V. S., & Colberg‐Poley, A. M. (2006) · Journal of Virology · doi:10.1128/jvi.00492-06 · Cited by 34 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895 · see citing works
Guo (2020) · doi:10.1186/s40779-020-00240-0 · Cited by 4,735 · see citing works
Interferon-stimulated genes: A complex web of host defenses
Schneider, W. M., Chevillotte, M. D., & Rice, C. M. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120231 · Cited by 3,067 · see citing works
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759 · see citing works
Self-citationRegulation and function of the cGAS–STING pathway of cytosolic DNA sensing
Chen, Q., Sun, L., & Chen, Z. J. (2016) · Nature Immunology · doi:10.1038/ni.3558 · Cited by 2,333 · see citing works
The cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309 · see citing works
Molecular mechanisms and cellular functions of cGAS–STING signalling
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052 · see citing works
Mitochondrial DNA stress primes the antiviral innate immune response
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. (2015) · Nature · doi:10.1038/nature14156 · Cited by 1,975 · see citing works
Immune Signaling by RIG-I-like Receptors
Loo, Y.-M., & Gale, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.003 · Cited by 1,875 · see citing works
CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.
Ablasser, A., Goldeck, M., Cavlar, T., Deimling, T., Witte, G., Röhl, I., Hopfner, K.-P., Ludwig, J., & Hornung, V. (2013) · Nature · doi:10.1038/nature12306 · Cited by 1,695 · see citing works
IFI16 is an innate immune sensor for intracellular DNA
Unterholzner, L., Keating, S. E., Baran, M., Horan, K. A., Jensen, S. B., Sharma, S., Sirois, C. M., Jin, T., Latz, E., Xiao, T. S., et al. (2010) · Nature Immunology · doi:10.1038/ni.1932 · Cited by 1,643 · see citing works
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
STING is a direct innate immune sensor of cyclic di-GMP
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
Corrales, L., Glickman, L. H., McWhirter, S. M., Kanne, D. B., Sivick, K. E., Katibah, G. E., Woo, S.-R., Lemmens, E., Banda, T., Leong, J. J., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.031 · Cited by 1,560 · see citing works
DNA sensing by the cGAS–STING pathway in health and disease
Motwani, M., Pesiridis, S., & Fitzgerald, K. A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0151-1 · Cited by 1,467 · see citing works
Spranger, S., Dai, D., Horton, B., & Gajewski, T. F. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.04.003 · Cited by 1,441 · see citing works
Mitochondria in innate immune responses
West, A. P., Shadel, G. S., & Ghosh, S. (2011) · Nature Reviews Immunology · doi:10.1038/nri2975 · Cited by 1,376 · see citing works
RETRACTED ARTICLE: Parkin and PINK1 mitigate STING-induced inflammation
Sliter, D. A., Martinez, J., Hao, L., Chen, X., Sun, N., Fischer, T. D., Burman, J. L., Li, Y., Zhang, Z., Narendra, D. P., et al. (2018) · Nature · doi:10.1038/s41586-018-0448-9 · Cited by 1,287 · see citing works
RetractedThe cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer
Li, T., & Chen, Z. J. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180139 · Cited by 1,293 · see citing works
Cytoplasmic chromatin triggers inflammation in senescence and cancer
Dou, Z., Ghosh, K., Vizioli, M. G., Zhu, J., Sen, P., Wangensteen, K. J., Simithy, J., Lan, Y., Lin, Y., Zhou, Z., et al. (2017) · Nature · doi:10.1038/nature24050 · Cited by 1,335 · see citing works
Self-citationSTING: infection, inflammation and cancer.
Barber, G. N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3921 · Cited by 1,313 · see citing works
Self-citationStructural basis of STING binding with and phosphorylation by TBK1
Zhang, C., Shang, G., Gui, X., Zhang, X., Bai, X.-C., & Chen, Z. J. (2019) · Nature · doi:10.1038/s41586-019-1000-2 · Cited by 1,095 · see citing works
Gao, P., Ascano, M., Wu, Y., Barchet, W., Gaffney, B. L., Zillinger, T., Serganov, A. A., Liu, Y., Jones, R. A., Hartmann, G., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.046 · Cited by 1,101 · see citing works
Harnessing innate immunity in cancer therapy
Demaria, O., Cornen, S., Daëron, M., Morel, Y., Medzhitov, R., & Vivier, E. (2019) · Nature · doi:10.1038/s41586-019-1593-5 · Cited by 957 · see citing works
Mitochondria in the Regulation of Innate and Adaptive Immunity
Weinberg, S. E., Sena, L. A., & Chandel, N. S. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.002 · Cited by 960 · see citing works
Design of amidobenzimidazole STING receptor agonists with systemic activity
Ramanjulu, J. M., Pesiridis, G. S., Yang, J., Concha, N., Singhaus, R., Zhang, S.-Y., Tran, J.-L., Moore, P., Lehmann, S., Eberl, H. C., et al. (2018) · Nature · doi:10.1038/s41586-018-0705-y · Cited by 912 · see citing works
Wang, C., Guan, Y., Lv, M., Zhang, R., Guo, Z., Wei, X., Du, X., Yang, J., Li, T., Wan, Y., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.017 · Cited by 869 · see citing works
Diner, E. J., Burdette, D. L., Wilson, S. C., Monroe, K. M., Kellenberger, C. A., Hyodo, M., Hayakawa, Y., Hammond, M. C., & Vance, R. E. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.05.009 · Cited by 767 · see citing works
Abe, T., & Barber, G. N. (2014) · Journal of Virology · doi:10.1128/jvi.00037-14 · Cited by 767 · see citing works
Self-citationHärtlova, A., Erttmann, S. F., Raffi, F. A., Schmalz, A. M., Resch, U., Anugula, S., Lienenklaus, S., Nilsson, L. M., Kröger, A., Nilsson, J. A., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.01.012 · Cited by 716 · see citing works
Mitochondria: master regulators of danger signalling
Galluzzi, L., Kepp, O., & Kroemer, G. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3479 · Cited by 733 · see citing works
cGAS-STING, an important pathway in cancer immunotherapy
Jiang, M., Chen, P., Wang, L., Li, W., Chen, B., Liu, Y., Wang, H., Zhao, S., Ye, L., He, Y., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00916-z · Cited by 647 · see citing works
Jensen, S., & Thomsen, A. R. (2012) · Journal of Virology · doi:10.1128/jvi.05738-11 · Cited by 604 · see citing works
Xia, T., Konno, H., Ahn, J., & Barber, G. N. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.029 · Cited by 589 · see citing works
Self-citationMitochondrial Damage Causes Inflammation via cGAS-STING Signaling in Acute Kidney Injury
Maekawa, H., Inoue, T., Ouchi, H., Jao, T.-M., Inoue, R., Nishi, H., Fujii, R., Ishidate, F., Tanaka, T., Tanaka, Y., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.050 · Cited by 586 · see citing works
PARP inhibition elicits STING-dependent antitumor immunity in brca1-deficient ovarian cancer
Ding, L., Kim, H.-J., Wang, Q., Kearns, M., Jiang, T., Ohlson, C. E., Li, B. B., Xie, S., Liu, J. F., Stover, E. H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.054 · Cited by 572 · see citing works
“Upon recognition of pathogenic or self-DNA, the cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) produces the second messenger cGAMP, which in turn activates stimulator of interferon genes (STING) signaling and subsequent production of type I interferons (IFNs) and pro-inflammatory cytokines (Ishikawa and…”
BackgroundNucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577 · see citing works
cGAS is essential for the antitumor effect of immune checkpoint blockade
Wang, H., Hu, S., Chen, X., Shi, H., Chen, C., Sun, L., & Chen, Z. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621363114 · Cited by 563 · see citing works
Jeremiah, N., Neven, B., Gentili, M., Callebaut, I., Maschalidi, S., Stolzenberg, M.-C., Goudin, N., Frémond, M.-L., Nitschke, P., Molina, T. J., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci79100 · Cited by 562 · see citing works
IFI16 DNA Sensor Is Required for Death of Lymphoid CD4 T Cells Abortively Infected with HIV
Monroe, K. M., Yang, Z., Johnson, J. R., Geng, X., Doitsh, G., Krogan, N. J., & Greene, W. C. (2014) · Science · doi:10.1126/science.1243640 · Cited by 511 · see citing works
Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine
Li, C., Lee, A., Grigoryan, L., Arunachalam, P. S., Scott, M. K. D., Trisal, M., Wimmers, F., Sanyal, M., Weidenbacher, P. A., Feng, Y., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01163-9 · Cited by 505 · see citing works
STING and the innate immune response to nucleic acids in the cytosol
Burdette, D. L., & Vance, R. E. (2013) · Nature Immunology · doi:10.1038/ni.2491 · Cited by 501 · see citing works
Mitochondria and cell signalling
Tait, S. W. G., & Green, D. R. (2012) · Journal of Cell Science · doi:10.1242/jcs.099234 · Cited by 453 · see citing works
STING: a master regulator in the cancer-immunity cycle
Zhu, Y., An, X., Zhang, X., Qiao, Y., Zheng, T., & Li, X. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1087-y · Cited by 431 · see citing works
Luo, X., Li, H., Ma, L., Zhou, J., Guo, X., Woo, S.-L., Pei, Y., Knight, L. R., Deveau, M., Chen, Y., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.09.010 · Cited by 415 · see citing works
Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy
Li, A., Yi, M., Qin, S., Song, Y., Chu, Q., & Wu, K. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0721-x · Cited by 413 · see citing works
Mitochondria in innate immune signaling
Banoth, B., & Cassel, S. L. (2018) · Translational Research · doi:10.1016/j.trsl.2018.07.014 · Cited by 410 · see citing works
SLC19A1 transports immunoreactive cyclic dinucleotides.
Luteijn, R. D., Zaver, S. A., Gowen, B. G., Wyman, S. K., Garelis, N. E., Onia, L., McWhirter, S. M., Katibah, G. E., Corn, J. E., Woodward, J. J., et al. (2019) · Nature · doi:10.1038/s41586-019-1553-0 · Cited by 379 · see citing works
Immunological impact of cell death signaling driven by radiation on the tumor microenvironment
Rodriguez-Ruiz, M. E., Vitale, I., Harrington, K. J., Melero, I., & Galluzzi, L. (2020) · Nature Immunology · doi:10.1038/s41590-019-0561-4 · Cited by 385 · see citing works
Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity
Dai, J., Huang, Y.-J., He, X., Zhao, M., Wang, X., Liu, Z.-S., Xue, W., Cai, H., Zhan, X.-Y., Huang, S.-Y., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.016 · Cited by 371 · see citing works
Takahashi, A., Loo, T. M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G. N., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03555-8 · Cited by 350 · see citing works
Self-citationImpact of mRNA chemistry and manufacturing process on innate immune activation
Nelson, J., Sorensen, E. W., Mintri, S., Rabideau, A. E., Zheng, W., Besin, G., Khatwani, N., Su, S. V., Miracco, E. J., Issa, W. J., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz6893 · Cited by 354 · see citing works
The Roles of Type I Interferon in Bacterial Infection
Boxx, G. M., & Cheng, G. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.05.016 · Cited by 335 · see citing works
Photoimmunology: how ultraviolet radiation affects the immune system
Bernard, J. J., Gallo, R. L., & Krutmann, J. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0185-9 · Cited by 329 · see citing works
Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway
Castanier, C., Garcin, D., Vazquez, A., & Arnoult, D. (2010) · The EMBO Reports · doi:10.1038/embor.2009.258 · Cited by 316 · 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
Immunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy
Riera-Domingo, C., Audigé, A., Granja, S., Cheng, W.-C., Ho, P.-C., Baltazar, F., Stockmann, C., & Mazzone, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00018.2019 · Cited by 310 · 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
The function and clinical application of extracellular vesicles in innate immune regulation
Zhou, X., Xie, F., Wang, L., Zhang, L., Zhang, S., Fang, M., & Zhou, F. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-0391-1 · Cited by 294 · 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
Olagnier, D., Brandtoft, A. M., Gunderstofte, C., Villadsen, N. L., Krapp, C., Thielke, A. L., Laustsen, A., Peri, S., Hansen, A. L., Bonefeld, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05861-7 · Cited by 282 · see citing works
Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response
Wan, D., Jiang, W., & Hao, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00615 · Cited by 270 · 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
Mitofusin 2 Inhibits Mitochondrial Antiviral Signaling
Yasukawa, K., Oshiumi, H., Takeda, M., Ishihara, N., Yanagi, Y., Seya, T., Kawabata, S.-I., & Koshiba, T. (2009) · Science Signaling · doi:10.1126/scisignal.2000287 · Cited by 255 · see citing works
Structural basis for the inhibition of cGAS by nucleosomes
Kujirai, T., Zierhut, C., Takizawa, Y., Kim, R., Negishi, L., Uruma, N., Hirai, S., Funabiki, H., & Kurumizaka, H. (2020) · Science · doi:10.1126/science.abd0237 · Cited by 243 · 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
STING mediates neurodegeneration and neuroinflammation in nigrostriatal α-synucleinopathy
Hinkle, J. T., Patel, J., Panicker, N., Karuppagounder, S. S., Biswas, D., Belingon, B., Chen, R., Brahmachari, S., Pletnikova, O., Troncoso, J. C., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2118819119 · Cited by 240 · see citing works
Structural basis of nucleosome-dependent cGAS inhibition
Boyer, J. A., Spangler, C. J., Strauss, J. D., Cesmat, A. P., Liu, P., McGinty, R. K., & Zhang, Q. (2020) · Science · doi:10.1126/science.abd0609 · Cited by 238 · see citing works
Organelle-specific initiation of cell death
Galluzzi, L., Bravo-San Pedro, J. M., & Kroemer, G. (2014) · Nature Cell Biology · doi:10.1038/ncb3005 · Cited by 239 · see citing works
Sweeten PAMPs: Role of sugar complexed PAMPs in innate immunity and vaccine biology
Mahla, R. S. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00248 · Cited by 239 · see citing works
Loo, T. M., Miyata, K., Tanaka, Y., & Takahashi, A. (2020) · Cancer Science · doi:10.1111/cas.14266 · Cited by 232 · see citing works
Human TBK1: A Gatekeeper of Neuroinflammation
Ahmad, L., Zhang, S.-Y., Casanova, J.-L., & Sancho-Shimizu, V. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.04.006 · Cited by 208 · see citing works
An, X., Zhu, Y., Zheng, T., Wang, G., Zhang, M., Li, J., Ji, H., Li, S., Yang, S., Xu, D., et al. (2019) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2018.11.003 · Cited by 188 · 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
Analysis of Drosophila STING Reveals an Evolutionarily Conserved Antimicrobial Function
Martin, M., Hiroyasu, A., Guzman, R. M., Roberts, S. A., & Goodman, A. G. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.05.029 · Cited by 173 · see citing works
Mathur, V., Burai, R., Vest, R. T., Bonanno, L. N., Lehallier, B., Zardeneta, M. E., Mistry, K. N., Do, D., Marsh, S. E., Abud, E. M., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.032 · Cited by 175 · see citing works
Similarities and interplay between senescent cells and macrophages
Behmoaras, J., & Gil, J. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202010162 · Cited by 158 · 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
Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders
Huang, Y., Liu, B., Sinha, S. C., Amin, S., & Gan, L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00672-x · Cited by 164 · see citing works
Mitochondrial DNA as an inflammatory mediator in cardiovascular diseases
Nakayama, H., & Otsu, K. (2018) · Biochemical Journal · doi:10.1042/bcj20170714 · Cited by 160 · see citing works
Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease
Sharma, M., Rajendrarao, S., Shahani, N., Ramírez-Jarquín, U. N., & Subramaniam, S. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002144117 · Cited by 155 · see citing works
Zou, M., Ke, Q., Nie, Q., Qi, R., Zhu, X., Liu, W., Hu, X., Sun, Q., Fu, J.-L., Tang, X., et al. (2022) · Cell Death & Differentiation · doi:10.1038/s41418-022-00967-4 · Cited by 138 · see citing works
PARP1 inhibitors trigger innate immunity via PARP1 trapping-induced DNA damage response
Kim, C., Wang, X.-D., & Yu, Y. (2020) · eLife · doi:10.7554/elife.60637 · Cited by 136 · see citing works
Strategies Used by Bacteria to Grow in Macrophages
Mitchell*, G., Chen*, C., & Portnoy, D. A. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.mchd-0012-2015 · Cited by 137 · see citing works
Mitochondria as a centrally positioned hub in the innate immune response
Sandhir, R., Halder, A., & Sunkaria, A. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.10.020 · Cited by 135 · see citing works
Reinert, L. S., Rashidi, A. S., Tran, D. N., Katzilieris-Petras, G., Hvidt, A. K., Gohr, M., Fruhwürth, S., Bodda, C., Thomsen, M. K., Vendelbo, M. H., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci136824 · Cited by 118 · see citing works
Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids
Hu, M.-M., & Shu, H.-B. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062903 · Cited by 110 · see citing works
TBK1, a central kinase in innate immune sensing of nucleic acids and beyond
Zhou, R., Zhang, Q., & Xu, P. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa051 · Cited by 104 · see citing works
A Nuclear Export Signal Is Required for cGAS to Sense Cytosolic DNA
Sun, H., Huang, Y., Mei, S., Xu, F., Liu, X., Zhao, F., Yin, L., Zhang, D., Wei, L., Wu, C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108586 · Cited by 105 · see citing works
Molecular and Structural Basis of DNA Sensors in Antiviral Innate Immunity
Zahid, A., Ismail, H., Li, B., & Jin, T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.613039 · Cited by 100 · see citing works
Diner, B. A., Lum, K. K., Javitt, A., & Cristea, I. M. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.047068 · Cited by 93 · see citing works
Epigenetic state determines the in vivo efficacy of STING agonist therapy
Falahat, R., Berglund, A., Perez-Villarroel, P., Putney, R. M., Hamaidi, I., Kim, S., Pilon-Thomas, S., Barber, G. N., & Mulé, J. J. (2023) · Nature Communications · doi:10.1038/s41467-023-37217-1 · Cited by 94 · see citing works
Self-citationCGAS is a micronucleophagy receptor for the clearance of micronuclei
Zhao, M., Wang, F., Wu, J., Cheng, Y., Cao, Y., Wu, X., Ma, M., Tang, F., Liu, Z., Liu, H., et al. (2021) · Autophagy · doi:10.1080/15548627.2021.1899440 · Cited by 89 · see citing works
Type I interferons and endoplasmic reticulum stress in health and disease
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.10.004 · Cited by 83 · see citing works
Bode, C., Fox, M., Tewary, P., Steinhagen, A., Ellerkmann, R. K., Klinman, D., Baumgarten, G., Hornung, V., & Steinhagen, F. (2016) · European Journal of Immunology · doi:10.1002/eji.201546113 · Cited by 79 · see citing works
Deb, P., Dai, J., Singh, S., Kalyoussef, E., & Fitzgerald-Bocarsly, P. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1800933 · Cited by 72 · see citing works
Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action
Shi, H.-X., Liu, X., Wang, Q., Tang, P.-P., Liu, X.-Y., Shan, Y.-F., & Wang, C. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002057 · Cited by 67 · see citing works
Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function
Imanishi, T., Unno, M., Kobayashi, W., Yoneda, N., Matsuda, S., Ikeda, K., Hoshii, T., Hirao, A., Miyake, K., Barber, G. N., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201800282 · Cited by 62 · see citing works
Self-citationHwang, I., Uchida, H., Dai, Z., Li, F., Sanchez, T., Locasale, J. W., Cantley, L. C., Zheng, H., & Paik, J. (2021) · Nature Communications · doi:10.1038/s41467-020-20839-0 · Cited by 61 · see citing works
Li, K., Gong, Y., Qiu, D., Tang, H., Zhang, J., Yuan, Z., Huang, Y., Qin, Y., Ye, L., & Yang, Y. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-004006 · Cited by 58 · see citing works
- Authors
- Ishikawa, H., & Barber, G. N.
- Affiliations
- University of Miami (US)
- Corresponding author
- Barber, Glen N.
- Venue
- Nature
- Published
- 2008-08-24
- Volume
- 455
- Issue
- 7213
- Pages
- 674-678
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2804933
- OpenAlex
- W2060004514
- Semantic Scholar
- cd831bfb6fd9847baedbe5161ddd21d405728bee
- Cited by
- 3,576
- References
- 29
- Citations by year
- 2026: 310 · 2025: 394 · 2024: 359 · 2023: 332 · 2022: 322 · 2021: 315 · 2020: 270 · 2019: 195 · 2018: 163 · 2017: 161 · 2016: 115 · 2015: 118 · 2014: 112 · 2013: 123 · 2012: 83
- FWCI
- 28.23
- Type
- journal article
- Language
- en
- Update notices
- erratum (2008-11-13)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI079336)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Keywords
- STING, endoplasmic reticulum, innate immunity, interferon-beta, IRF3, NF-κB, RIG-I, Sec61β, translocon, TRAP complex, vesicular stomatitis virus, herpesvirus, negative-strand RNA viruses, viral DNA sensing, antiviral defense, protein translocation, pattern recognition receptors
- MeSH terms
- STING Protein, Animals, Cell Line, Endoplasmic Reticulum, Fibroblasts, Humans, Immunity, Innate, Interferons, Membrane Proteins, Mice, Inbred C57BL, Signal Transduction, Mice, Knockout, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
