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dc.contributor.authorBudanov, Andrei
dc.contributor.authorParmigiani, Anita
dc.contributor.authorNourbakhsh, Aida
dc.contributor.authorDing, Boxiao
dc.contributor.authorWang, Wei
dc.contributor.authorKim, Young Chul
dc.contributor.authorAkopiants, Konstantin
dc.contributor.authorGuan, Kun-Liang
dc.contributor.authorKarin, Michael
dc.date.accessioned2020-02-26T17:00:38Z
dc.date.available2020-02-26T17:00:38Z
dc.date.issued2014
dc.date.submitted2014en
dc.identifier.citationParmigiani, A., Nourbakhsh, A., Ding, B., Wang, W., Kim, Y.C., Akopiants, K., Guan, K.L., Karin, M. & Budanov, A.V., Sestrins inhibit mTORC1 kinase activation through the GATOR complex., Cell Reports, 9, 4, 2014, 1281 - 1291en
dc.identifier.otherY
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S2211124714008730?via%3Dihub#!
dc.identifier.urihttp://hdl.handle.net/2262/91629
dc.description.abstractThe mechanistic target of rapamycin complex 1 (mTORC1) kinase is a sensor of different environmental conditions and regulator of cell growth, metabolism, and autophagy. mTORC1 is activated by Rag GTPases, working as RagA:RagB and RagC:RagD heterodimers. Rags control mTORC1 activity by tethering mTORC1 to the lysosomes where it is activated by Rheb GTPase. RagA:RagB, active in its GTP-bound form, is inhibited by GATOR1 complex, a GTPase-activating protein, and GATOR1 is in turn negatively regulated by GATOR2 complex. Sestrins are stress-responsive proteins that inhibit mTORC1 via activation of AMP-activated protein kinase (AMPK) and tuberous sclerosis complex. Here we report an AMPK-independent mechanism of mTORC1 inhibition by Sestrins mediated by their interaction with GATOR2. As a result of this interaction, the Sestrins suppress mTOR lysosomal localization in a Rag-dependent manner. This mechanism is potentially involved in mTORC1 regulation by amino acids, rotenone, and tunicamycin, connecting stress response with mTORC1 inhibition.en
dc.format.extent1281en
dc.format.extent1291en
dc.language.isoenen
dc.relation.ispartofseriesCell Reports;
dc.relation.ispartofseries9;
dc.relation.ispartofseries4;
dc.rightsYen
dc.subjectSestrinsen
dc.subjectCell growthen
dc.subjectMetabolismen
dc.titleSestrins inhibit mTORC1 kinase activation through the GATOR complex.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/budanova
dc.identifier.rssinternalid156245
dc.identifier.doi10.1016/j.celrep.2014.10.019
dc.rights.ecaccessrightsopenAccess
dc.relation.sourcewebpageen
dc.subject.TCDThemeAgeingen
dc.subject.TCDThemeCanceren
dc.subject.TCDTagMetabolismen
dc.subject.TCDTagPHOSPHORYLATIONen
dc.relation.sourceurihttps://www.sciencedirect.com/science/article/pii/S2211124714008730?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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