Cited by 3,576interferon and immune responsesImmune Response and InflammationEndoplasmic Reticulum Stress and Disease

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STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling

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Ishikawa, Hiroki, Barber, Glen N.·2008·Nature

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Abstract

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.

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Authors: Ishikawa, H., & Barber, G. N.
Affiliations: University of Miami (US)
Corresponding author: Barber, Glen N.
ORCID: Ishikawa, Hiroki
Barber, Glen N.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2008-08-24
Volume: 455
Issue: 7213
Pages: 674-678
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature07317
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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

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STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling

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