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dc.contributor.authorMalzer, Elkeen
dc.contributor.authorDominicus, Caia Sen
dc.contributor.authorChambers, Josephen
dc.contributor.authorDickens, Jenniferen
dc.contributor.authorMookerjee, Souradipen
dc.contributor.authorMarciniak, Stefanen
dc.date.accessioned2018-05-24T16:33:41Z
dc.date.available2018-05-24T16:33:41Z
dc.date.issued2018-04-03en
dc.identifier.issn1741-7007
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/276162
dc.description.abstractBackground: Developmental pathways must be responsive to the environment. Phosphorylation of eIF2α enables a family of stress sensing kinases to trigger the integrated stress response (ISR), which has pro-survival and developmental consequences. Bone Morphogenetic Proteins (BMPs) regulate multiple developmental processes in organisms from insects to mammals. Results: Here we show in Drosophila that GCN2 antagonises BMP signaling through direct effects on translation and indirectly via the transcription factor crc (dATF4). Expression of a constitutively active GCN2 or loss of the eIF2α phosphatase dPPP1R15 impair developmental BMP signaling in flies. In cells, inhibition of translation by GCN2 blocks downstream BMP signaling. Moreover, loss of d4E-BP, a target of crc, augments BMP signaling in vitro and rescues tissue development in vivo. Conclusion: These results identify a novel mechanism by which the ISR modulates BMP signaling during development.
dc.format.mediumElectronicen
dc.languageengen
dc.publisherBioMed Central
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAnimalsen
dc.subjectDrosophilaen
dc.subjectProtein Kinasesen
dc.subjectDrosophila Proteinsen
dc.subjectBone Morphogenetic Proteinsen
dc.subjectEukaryotic Initiation Factor-2en
dc.subjectSignal Transductionen
dc.subjectGene Expression Regulationen
dc.subjectPhosphorylationen
dc.titleThe integrated stress response regulates BMP signalling through effects on translation.en
dc.typeArticle
prism.issueIdentifier1en
prism.publicationDate2018en
prism.publicationNameBMC biologyen
prism.startingPage34
prism.volume16en
dc.identifier.doi10.17863/CAM.23445
dcterms.dateAccepted2018-03-08en
rioxxterms.versionofrecord10.1186/s12915-018-0503-xen
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-04-03en
dc.contributor.orcidChambers, Joseph [0000-0003-4675-0053]
dc.contributor.orcidMookerjee, Souradip [0000-0003-4904-1324]
dc.contributor.orcidMarciniak, Stefan [0000-0001-8472-7183]
dc.identifier.eissn1741-7007
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G1002610)
pubs.funder-project-idAcademy of Medical Sciences (unknown)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (3819-1617-14)
pubs.funder-project-idAddenbrooke's Charitable Trust (ACT) (13/17 B(v) 900908/9980)
pubs.funder-project-idMRC (MR/R009120/1)
pubs.funder-project-idMRC (G0601840)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idWellcome Trust (093026/Z/10/Z)
cam.orpheus.successThu Jan 30 12:59:12 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International