The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
STING Activation by Translocation from the ER Is Associated with Infection and Autoinflammatory Disease
Open accessAbstract
SUMMARY STING is an ER-associated membrane protein that is critical for innate-immune sensing of pathogens. STING-mediated activation of the IFN-I pathway through the TBK1/IRF3 signaling axis involves both cyclic-dinucleotide binding, and its translocation from the ER to vesicles. However, how these events are coordinated, and the exact mechanism of STING activation, remain poorly understood. Here, we found that the Shigella effector protein IpaJ potently inhibits STING signaling by blocking its translocation from the ER to ERGIC, even in the context of dinucleotide binding. Reconstitution using purified components revealed STING translocation as the rate-limiting event in maximal signal transduction. Furthermore, STING mutations associated with autoimmunity in humans were found to cause constitutive ER exit, and to activate STING independent of cGAMP binding. Together, these data provide compelling evidence for an ER-retention and ERGIC/Golgi-trafficking mechanism of STING regulation that is subverted by bacterial pathogens and is deregulated in human genetic disease.
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Cites
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 · cited 5×
“’’ To then confirm previous results (Ishikawa et al., 2009) that BFA inhibits STING signaling in our model system, we treated MEFs with increasing doses of BFA or nocodazole for 1 hr and transfected DNA to activate STING signaling and IFN expression.”
InfluentialSTING 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
Activated STING in a Vascular and Pulmonary Syndrome
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. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1312625 · Cited by 1,412
Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects
Li, X.-D., Wu, J., Gao, D., Wang, H., Sun, L., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1244040 · Cited by 1,113
Zhang, X., Shi, H., Wu, J., Zhang, X., Sun, L., Chen, C., & Chen, Z. J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.05.022 · Cited by 1,071
Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses
Gao, D., Wu, J., Wu, Y.-T., Du, F., Aroh, C., Yan, N., Sun, L., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1240933 · Cited by 992
Self-citationThe cGAS-cGAMP-STING Pathway of Cytosolic DNA Sensing and Signaling
Cai, X., Chiu, Y.-H., & Chen, Z. J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.040 · Cited by 988
Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response
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
Woodward, J. J., Iavarone, A. T., & Portnoy, D. A. (2010) · Science · doi:10.1126/science.1189801 · Cited by 810
Konno, H., Konno, K., & Barber, G. N. (2013) · Cell · doi:10.1016/j.cell.2013.09.049 · Cited by 687
Cited by
Regulation 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
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
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
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
cGAS in action: Expanding roles in immunity and inflammation
Ablasser, A., & Chen, Z. J. (2019) · Science · doi:10.1126/science.aat8657 · Cited by 1,077
Metadata
- Authors
- Dobbs, N., Burnaevskiy, N., Chen, D., Gonugunta, V. K., Alto, N. M., & Yan, N.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 18
- Issue
- 2
- Pages
- 157-168
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W1776390480
- Cited by
- 630
- References
- 28
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Dobbs, N., Burnaevskiy, N., Chen, D., Gonugunta, V. K., Alto, N. M., & Yan, N. (2015). STING Activation by Translocation from the ER Is Associated with Infection and Autoinflammatory Disease. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2015.07.001
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