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dc.contributor.authorThomas, Sally E
dc.contributor.authorMalzer, Elke
dc.contributor.authorOrdóñez, Adriana
dc.contributor.authorDalton, Lucy E
dc.contributor.authorvan T Wout, Emily FA
dc.contributor.authorLiniker, Elizabeth
dc.contributor.authorCrowther, Damian C
dc.contributor.authorLomas, David A
dc.contributor.authorMarciniak, Stefan J
dc.date.accessioned2019-02-12T15:35:56Z
dc.date.available2019-02-12T15:35:56Z
dc.date.issued2013-03-15
dc.identifier.issn0021-9258
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/289300
dc.description.abstractCell cycle checkpoints ensure that proliferation occurs only under permissive conditions, but their role in linking nutrient availability to cell division is incompletely understood. Protein folding within the endoplasmic reticulum (ER) is exquisitely sensitive to energy supply and amino acid sources because deficiencies impair luminal protein folding and consequently trigger ER stress signaling. Following ER stress, many cell types arrest within the G(1) phase, although recent studies have identified a novel ER stress G(2) checkpoint. Here, we report that ER stress affects cell cycle progression via two classes of signal: an early inhibition of protein synthesis leading to G(2) delay involving CHK1 and a later induction of G(1) arrest associated both with the induction of p53 target genes and loss of cyclin D(1). We show that substitution of p53/47 for p53 impairs the ER stress G(1) checkpoint, attenuates the recovery of protein translation, and impairs induction of NOXA, a mediator of cell death. We propose that cell cycle regulation in response to ER stress comprises redundant pathways invoked sequentially first to impair G(2) progression prior to ultimate G(1) arrest.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.subjectCell Line
dc.subjectCell Line, Tumor
dc.subjectHela Cells
dc.subjectEndoplasmic Reticulum
dc.subjectAnimals
dc.subjectHumans
dc.subjectDrosophila melanogaster
dc.subjectFlow Cytometry
dc.subjectCell Separation
dc.subjectCell Cycle
dc.subjectCell Proliferation
dc.subjectProtein Biosynthesis
dc.subjectGene Expression Regulation
dc.subjectRNA Interference
dc.subjectGenes, p53
dc.subjectPlasmids
dc.subjectTumor Suppressor Protein p53
dc.subjectProtein Phosphatase 1
dc.subjectHEK293 Cells
dc.titlep53 and translation attenuation regulate distinct cell cycle checkpoints during endoplasmic reticulum (ER) stress.
dc.typeArticle
prism.endingPage7617
prism.issueIdentifier11
prism.publicationDate2013
prism.publicationNameJ Biol Chem
prism.startingPage7606
prism.volume288
dc.identifier.doi10.17863/CAM.23200
rioxxterms.versionofrecord10.1074/jbc.M112.424655
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2013-03
dc.contributor.orcidMarciniak, Stefan [0000-0001-8472-7183]
dc.identifier.eissn1083-351X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (G0700990)
pubs.funder-project-idMedical Research Council (G1002610)
pubs.funder-project-idMedical Research Council (G0901786)
pubs.funder-project-idMedical Research Council (G0601840)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idWellcome Trust (089703/Z/09/Z)
cam.issuedOnline2013-01-22


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