Almine, JF, O’Hare, CAJ, Dunphy, G, Haga, IR, Naik, RJ, Atrih, A, Connolly, DJ, Taylor, J, Kelsall, IR, Bowie, AG, Beard, PM and Unterholzner, L (2017) IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes. Nature Communications, 8 (1). ISSN 2041-1723

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Abstract

<jats:title>Abstract</jats:title><jats:p>Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). Other putative DNA receptors have been described, but whether their functions are redundant, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear. Here we show that interferon-γ inducible protein 16 (IFI16) cooperates with cGAS during DNA sensing in human keratinocytes, as both cGAS and IFI16 are required for the full activation of an innate immune response to exogenous DNA and DNA viruses. IFI16 is also required for the cGAMP-induced activation of STING, and interacts with STING to promote STING phosphorylation and translocation. We propose that the two DNA sensors IFI16 and cGAS cooperate to prevent the spurious activation of the type I interferon response.</jats:p>

Item Type: Article
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Subjects: Q Science > QD Chemistry > QD415 Biochemistry
R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
Divisions: Faculty of Natural Sciences > School of Life Sciences
Depositing User: Symplectic
Date Deposited: 07 Feb 2023 08:30
Last Modified: 07 Feb 2023 08:30
URI: https://eprints.keele.ac.uk/id/eprint/11893

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