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dc.contributor.authorBudanov, Andrei
dc.contributor.authorKarin, Michael
dc.date.accessioned2020-02-26T16:56:37Z
dc.date.available2020-02-26T16:56:37Z
dc.date.issued2008
dc.date.submitted2008en
dc.identifier.citationBudanov, A.V. & Karin, M., p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling., Cell, 134, 3, 2008, 451 - 460en
dc.identifier.issn0092-8674
dc.identifier.otherY
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0092867408007800?via%3Dihub
dc.identifier.urihttp://hdl.handle.net/2262/91628
dc.description.abstractThe tumor suppressor p53 is activated upon genotoxic and oxidative stress and in turn inhibits cell proliferation and growth through induction of specific target genes. Cell growth is positively regulated by mTOR, whose activity is inhibited by the TSC1:TSC2 complex. Although genotoxic stress has been suggested to inhibit mTOR via p53-mediated activation of mTOR inhibitors, the precise mechanism of this link was unknown. We now demonstrate that the products of two p53 target genes, Sestrin1 and Sestrin2, activate the AMP-responsive protein kinase (AMPK) and target it to phosphorylate TSC2 and stimulate its GAP activity, thereby inhibiting mTOR. Correspondingly, Sestrin2-deficient mice fail to inhibit mTOR signaling upon genotoxic challenge. Sestrin1 and Sestrin2 therefore provide an important link between genotoxic stress, p53 and the mTOR signaling pathway.en
dc.format.extent451en
dc.format.extent460en
dc.language.isoenen
dc.relation.ispartofseriesCell;
dc.relation.ispartofseries134;
dc.relation.ispartofseries3;
dc.rightsYen
dc.subjectTumour suppressionen
dc.subjectGenotoxic stressen
dc.subjectSestrinsen
dc.titlep53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signalingen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/budanova
dc.identifier.rssinternalid156254
dc.identifier.doi10.1016/j.cell.2008.06.028
dc.rights.ecaccessrightsopenAccess
dc.relation.sourcewebpageen
dc.subject.TCDThemeAgeingen
dc.subject.TCDThemeCanceren
dc.subject.TCDTagCELL GROWTHen
dc.subject.TCDTagPHOSPHORYLATIONen
dc.relation.sourceurihttps://www.sciencedirect.com/science/article/pii/S0092867408007800?via%3Dihuben
dc.identifier.orcid_id0000-0002-7943-1000
dc.subject.darat_impairmentAge-related disabilityen
dc.subject.darat_thematicHealthen
dc.status.accessibleNen


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