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dc.contributor.authorMURRAY, JAMESen
dc.date.accessioned2014-11-24T16:06:14Z
dc.date.available2014-11-24T16:06:14Z
dc.date.issued2013en
dc.date.submitted2013en
dc.identifier.citationPike, L.R.G., Singleton, D.C., Buffa, F., Abramczyk, O., Phadwal, K., Li, J.-L., Simon, A.K., Murray, J.T., Harris, A.L., Transcriptional up-regulation of ULK1 by ATF4 contributes to cancer cell survival, Biochemical Journal, 449, 2, 2013, 389-400en
dc.identifier.issn02646021en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/72159
dc.descriptionPUBLISHEDen
dc.description.abstractHypoxia in the microenvironment of many solid tumours is an important determinant of malignant progression. The ISR (integrated stress response) protects cells from the ER (endoplasmic reticulum) stress caused by severe hypoxia. Likewise, autophagy is a mechanism by which cancer cells can evade hypoxic cell death. In the present paper we report that the autophagy-initiating kinase ULK1 (UNC51-like kinase 1) is a direct transcriptional target of ATF4 (activating transcription factor 4), which drives the expression of ULK1 mRNA and protein in severe hypoxia and ER stress. We demonstrate that ULK1 is required for autophagy in severe hypoxia and that ablation of ULK1 causes caspase-3/7-independent cell death. Furthermore, we report that ULK1 expression is associated with a poor prognosis in breast cancer. Collectively, the findings of the present study identify transcriptional up-regulation of ULK1 as a novel arm of the ISR, and suggest ULK1 as a potentially effective target for cancer therapy.en
dc.description.sponsorshipThis work was supported by Cancer Research UK, the Rhodes Trust, the NIHR (National Institute for Health Research) Oxford Biomedical Research Centre, and the Natural Sciences and Engineering Research Council of Canadaen
dc.format.extent389-400en
dc.language.isoenen
dc.relation.ispartofseriesBiochemical Journalen
dc.relation.ispartofseries449en
dc.relation.ispartofseries2en
dc.rightsYen
dc.subjectunfolded protein response (UPR)en
dc.subjectUNC51-like kinase 1 (ULK1)en
dc.subjectintegrated stress responseen
dc.subjecthypoxiaen
dc.subjectendoplasmic reticulum stress,en
dc.subjectautophagy,en
dc.titleTranscriptional up-regulation of ULK1 by ATF4 contributes to cancer cell survivalen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/jmurray6en
dc.identifier.rssinternalid92572en
dc.identifier.doihttp://dx.doi.org/10.1042/BJ20120972en
dc.rights.ecaccessrightsOpenAccess
dc.subject.TCDThemeAgeingen
dc.subject.TCDThemeCanceren


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