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dc.contributor.authorSaveljeva, Svetlana
dc.contributor.authorCleary, Patricia
dc.contributor.authorMnich, Katarzyna
dc.contributor.authorAyo, Abiodun
dc.contributor.authorPakos-Zebrucka, Karolina
dc.contributor.authorPatterson, John B.
dc.contributor.authorLogue, Susan E.
dc.contributor.authorSamali, Afshin
dc.date.accessioned2018-09-20T16:23:55Z
dc.date.available2018-09-20T16:23:55Z
dc.date.issued2016-02-22
dc.identifier.citationSaveljeva, Svetlana; Cleary, Patricia; Mnich, Katarzyna; Ayo, Abiodun; Pakos-Zebrucka, Karolina; Patterson, John B. Logue, Susan E.; Samali, Afshin (2016). Endoplasmic reticulum stress-mediated induction of sestrin 2 potentiates cell survival. Oncotarget 7 (11), 12254-12266
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/10379/13802
dc.description.abstractUpregulation of SESTRIN 2 (SESN2) has been reported in response to diverse cellular stresses. In this study we demonstrate SESTRIN 2 induction following endoplasmic reticulum (ER) stress. ER stress-induced increases in SESTRIN 2 expression were dependent on both PERK and IRE1/XBP1 arms of the unfolded protein response (UPR). SESTRIN 2 induction, post ER stress, was responsible for mTORC1 inactivation and contributed to autophagy induction. Conversely, knockdown of SESTRIN 2 prolonged mTORC1 signaling, repressed autophagy and increased ER stress-induced cell death. Unexpectedly, the increase in ER stress-induced cell death was not linked to autophagy inhibition. Analysis of UPR pathways identified prolonged eIF2 alpha, ATF4 and CHOP signaling in SESTRIN 2 knockdown cells following ER stress. SESTRIN 2 regulation enables UPR derived signals to indirectly control mTORC1 activity shutting down protein translation thus preventing further exacerbation of ER stress.
dc.publisherImpact Journals, LLC
dc.relation.ispartofOncotarget
dc.subjectsestrin 2
dc.subjecter stress
dc.subjectupr
dc.subjectcell death
dc.subjectautophagy
dc.subjectunfolded protein response
dc.subjecter-stress
dc.subjecttranscriptional regulation
dc.subjectperk
dc.subjectautophagy
dc.subjectdeath
dc.subjectcarcinoma
dc.subjectapoptosis
dc.titleEndoplasmic reticulum stress-mediated induction of sestrin 2 potentiates cell survival
dc.typeArticle
dc.identifier.doi10.18632/oncotarget.7601
dc.local.publishedsourcehttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=7601&path%5B%5D=21993
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