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Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage

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Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage. / Dunphy, Gillian; Flannery, Sinead; Almine, Jessica et al.
In: Molecular Cell, Vol. 71, No. 5, 06.09.2018, p. 745-760.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Dunphy, G, Flannery, S, Almine, J, Connolly, D, Paulus, C, Jønsson, K, Jakobsen, M, Nevels, M, Bowie, A & Unterholzner, L 2018, 'Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage', Molecular Cell, vol. 71, no. 5, pp. 745-760. https://doi.org/10.1016/j.molcel.2018.07.034

APA

Dunphy, G., Flannery, S., Almine, J., Connolly, D., Paulus, C., Jønsson, K., Jakobsen, M., Nevels, M., Bowie, A., & Unterholzner, L. (2018). Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage. Molecular Cell, 71(5), 745-760. https://doi.org/10.1016/j.molcel.2018.07.034

Vancouver

Dunphy G, Flannery S, Almine J, Connolly D, Paulus C, Jønsson K et al. Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage. Molecular Cell. 2018 Sept 6;71(5):745-760. doi: 10.1016/j.molcel.2018.07.034

Author

Dunphy, Gillian ; Flannery, Sinead ; Almine, Jessica et al. / Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage. In: Molecular Cell. 2018 ; Vol. 71, No. 5. pp. 745-760.

Bibtex

@article{9f426f6e277f495397a6279f3551ab68,
title = "Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage",
abstract = "DNA damage can be sensed as a danger-associated molecular pattern by the innate immune system. Here we find that keratinocytes and other human cells mount an innate immune response within hours of Etoposide-induced DNA damage, which involves the DNA sensing adaptor STING, but is independent of the cytosolic DNA receptor cGAS. This non-canonical activation of STING is mediated by the DNA binding protein IFI16, together with the DNA damage response factors ATM and PARP-1, resulting in the assembly of an alternative STING signalling complex which includes the tumour suppressor p53 and the E3 ubiquitin ligase TRAF6. TRAF6 catalyses the formation of K63-linked ubiquitin chains on STING, leading to the activation of the transcription factor NF-κB, and the induction of an alternative STING-dependent gene expression program. We propose that STING acts as a signalling hub that co-ordinates a transcriptional response depending on its mode of activation.",
keywords = "innate immunity, DNA damage, etoposide, interferon, IFI16, STING, p53, TRAF6, ubiquitin",
author = "Gillian Dunphy and Sinead Flannery and Jessica Almine and Dympna Connolly and Christina Paulus and Kasper J{\o}nsson and Martin Jakobsen and Michael Nevels and Andrew Bowie and Leonie Unterholzner",
year = "2018",
month = sep,
day = "6",
doi = "10.1016/j.molcel.2018.07.034",
language = "English",
volume = "71",
pages = "745--760",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage

AU - Dunphy, Gillian

AU - Flannery, Sinead

AU - Almine, Jessica

AU - Connolly, Dympna

AU - Paulus, Christina

AU - Jønsson, Kasper

AU - Jakobsen, Martin

AU - Nevels, Michael

AU - Bowie, Andrew

AU - Unterholzner, Leonie

PY - 2018/9/6

Y1 - 2018/9/6

N2 - DNA damage can be sensed as a danger-associated molecular pattern by the innate immune system. Here we find that keratinocytes and other human cells mount an innate immune response within hours of Etoposide-induced DNA damage, which involves the DNA sensing adaptor STING, but is independent of the cytosolic DNA receptor cGAS. This non-canonical activation of STING is mediated by the DNA binding protein IFI16, together with the DNA damage response factors ATM and PARP-1, resulting in the assembly of an alternative STING signalling complex which includes the tumour suppressor p53 and the E3 ubiquitin ligase TRAF6. TRAF6 catalyses the formation of K63-linked ubiquitin chains on STING, leading to the activation of the transcription factor NF-κB, and the induction of an alternative STING-dependent gene expression program. We propose that STING acts as a signalling hub that co-ordinates a transcriptional response depending on its mode of activation.

AB - DNA damage can be sensed as a danger-associated molecular pattern by the innate immune system. Here we find that keratinocytes and other human cells mount an innate immune response within hours of Etoposide-induced DNA damage, which involves the DNA sensing adaptor STING, but is independent of the cytosolic DNA receptor cGAS. This non-canonical activation of STING is mediated by the DNA binding protein IFI16, together with the DNA damage response factors ATM and PARP-1, resulting in the assembly of an alternative STING signalling complex which includes the tumour suppressor p53 and the E3 ubiquitin ligase TRAF6. TRAF6 catalyses the formation of K63-linked ubiquitin chains on STING, leading to the activation of the transcription factor NF-κB, and the induction of an alternative STING-dependent gene expression program. We propose that STING acts as a signalling hub that co-ordinates a transcriptional response depending on its mode of activation.

KW - innate immunity

KW - DNA damage

KW - etoposide

KW - interferon

KW - IFI16

KW - STING

KW - p53

KW - TRAF6

KW - ubiquitin

U2 - 10.1016/j.molcel.2018.07.034

DO - 10.1016/j.molcel.2018.07.034

M3 - Journal article

VL - 71

SP - 745

EP - 760

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 5

ER -