The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Cytosolic sensing of immuno-stimulatory DNA, the enemy within
Open accessAbstract
In the cytoplasm, DNA is sensed as a universal danger signal by the innate immune system. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor/enzyme that catalyzes formation of 2'-5'-cGAMP, an atypical cyclic di-nucleotide second messenger that binds and activates the Stimulator of Interferon Genes (STING), resulting in recruitment of Tank Binding Kinase 1 (TBK1), activation of the transcription factor Interferon Regulatory Factor 3 (IRF3), and trans-activation of innate immune response genes, including type I Interferon cytokines (IFN-I). Activation of the pro-inflammatory cGAS-STING-IRF3 response is triggered by direct recognition of the DNA genomes of bacteria and viruses, but also during RNA virus infection, neoplastic transformation, tumor immunotherapy and systemic auto-inflammatory diseases. In these circumstances, the source of immuno-stimulatory DNA has often represented a fundamental yet poorly understood aspect of the response. This review focuses on recent findings related to cGAS activation by an array of self-derived DNA substrates, including endogenous retroviral elements, mitochondrial DNA (mtDNA) and micronuclei generated as a result of genotoxic stress and DNA damage. These findings emphasize the role of the cGAS axis as a cell-intrinsic innate immune response to a wide variety of genomic insults.
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“As this model would predict, knockdown of the cytosolic DNA sensing pathway components cGAS or STING17 inhibited the IFN-I response in both late senescent and 3X cells (Extended Data Fig. 5l and Fig. 7c, d), and also downregulated the SASP response in late senescent cells (Extended Data Fig. 7e).”
From L1 drives IFN in senescent cells and promotes age-associated inflammation (2019) · cites this paper as [17]
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Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
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HOW CELLS RESPOND TO INTERFERONS
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Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing
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STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors
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DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity
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cGAS surveillance of micronuclei links genome instability to innate immunity
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L1 drives IFN in senescent cells and promotes age-associated inflammation
De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., Boeke, J. D., et al. (2019) · Nature · doi:10.1038/s41586-018-0784-9 · Cited by 1,255
“The absolute average retrotransposition frequency (percentage of GFP-positive cells) was 4.1, which matches the published values for the reporter used (pLD143) 53 . l, Knockdowns of cGAS and STING were performed in senescent or 3X cells as with the other shRNAs (Fig.”
InfluentialDunphy, G., Flannery, S. M., Almine, J. F., Connolly, D. J., Paulus, C., Jønsson, K. L., Jakobsen, M. R., Nevels, M. M., Bowie, A. G., & Unterholzner, L. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.07.034 · Cited by 648
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
A Genetic Map of the Response to DNA Damage in Human Cells
Olivieri, M., Cho, T., Álvarez-Quilón, A., Li, K., Schellenberg, M. J., Zimmermann, M., Hustedt, N., Rossi, S. E., Adam, S., Melo, H., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.040 · Cited by 551
Biomolecular Condensates and Cancer
Boija, A., Klein, I. A., & Young, R. A. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.12.003 · Cited by 338
Metadata
- Authors
- Dhanwani, R., Takahashi, M., & Sharma, S.
- Affiliations
- La Jolla Institute for Immunology (US)
- Corresponding author
- Sharma, Sonia
- Venue
- Current Opinion in Immunology
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 50
- Pages
- 82-87
- ISSN
- 0952-7915 (ISSN-L)
- PMC
- PMC5916810
- OpenAlex
- W2771759088
- Cited by
- 123
- References
- 62
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 17 · 2023: 15 · 2022: 16 · 2021: 15 · 2020: 17 · 2019: 17 · 2018: 11
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA199376)
- 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 › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- cGAS-STING pathway, cytosolic DNA sensing, STING, IRF3, type I interferon, innate immunity, endogenous retroviruses, mitochondrial DNA, micronuclei, genotoxic stress, DNA damage, cancer immunotherapy, autoinflammatory disease, RNA virus infection, oncogenic transformation
- MeSH terms
- Animals, Antigens, Cytosol, DNA, DNA Damage, Humans, Immunity, Immunity, Innate, Infections, Inflammation, Neoplasms, Host-Pathogen Interactions
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