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dc.contributor.authorDunphy, Gillian
dc.contributor.authorFlannery, Sinéad M
dc.contributor.authorAlmine, Jessica F
dc.contributor.authorConnolly, Dympna J
dc.contributor.authorPaulus, Christina
dc.contributor.authorJonsson, Kasper L
dc.contributor.authorJakobsen, Martin R
dc.contributor.authorNevels, Michael Martin
dc.contributor.authorBowie, Andrew G
dc.contributor.authorUnterholzner, Leonie
dc.date.accessioned2018-09-17T11:30:06Z
dc.date.available2018-09-17T11:30:06Z
dc.date.issued2018-09-06
dc.identifier.citationDunphy , G , Flannery , S M , Almine , J F , Connolly , D J , Paulus , C , Jonsson , K L , Jakobsen , M R , Nevels , M M , Bowie , A G & 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 , e5 , pp. 745-760 . https://doi.org/10.1016/j.molcel.2018.07.034en
dc.identifier.issn1097-2765
dc.identifier.otherPURE: 255113043
dc.identifier.otherPURE UUID: e92f7d2b-b839-4c92-b0bd-4fbd2d175b5b
dc.identifier.otherScopus: 85052637604
dc.identifier.otherORCID: /0000-0002-7115-407X/work/48131995
dc.identifier.otherORCID: /0000-0002-4123-5629/work/48131998
dc.identifier.otherWOS: 000443829100009
dc.identifier.urihttp://hdl.handle.net/10023/16034
dc.descriptionThe work was supported by the Medical Research Council (Career Development Award MR/K00655X/1 to L.U. and a PhD studentship to G.D. through the MRC doctoral training program at the School of Life Sciences, University of Dundee), North West Cancer Research (project grant CR1140), and the European Commission (MC-CIG 631718). S.M.F., D.J.C., and A.G.B. were supported by Science Foundation Ireland (11/PI/1056) and the NIH (AI093752). C.P. and M.M.N. were supported by the Medical Research Council (MR/P022146/1). M.R.J. was supported by grants from the Danish Council for Independent Research, Lundbeck Foundation, and Aase og Ejnar Danielsens Fond.en
dc.description.abstractDNA 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 signaling complex that includes the tumor suppressor p53 and the E3 ubiquitin ligase TRAF6. TRAF6 catalyzes 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 signaling hub that coordinates a transcriptional response depending on its mode of activation.
dc.format.extent22
dc.language.isoeng
dc.relation.ispartofMolecular Cellen
dc.rights© 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en
dc.subjectInnate immunityen
dc.subjectDNA damageen
dc.subjectEtoposideen
dc.subjectInterferonen
dc.subjectIFI16en
dc.subjectSTINGen
dc.subjectp53en
dc.subjectTRAF6en
dc.subjectUbiquitinen
dc.subjectQR180 Immunologyen
dc.subjectDASen
dc.subjectBDCen
dc.subject.lccQR180en
dc.titleNon-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damageen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1016/j.molcel.2018.07.034
dc.description.statusPeer revieweden
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S1097276518306038?dgcid=raven_sd_search_email#app2en


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