Endoplasmic reticulum stress-mediated induction of sestrin 2 potentiates cell survival
Saveljeva, Svetlana Cleary, Patricia Mnich, Katarzyna Ayo, Abiodun Pakos-Zebrucka, Karolina Patterson, John B. Logue, Susan E. Samali, Afshin
Saveljeva, Svetlana
Cleary, Patricia
Mnich, Katarzyna
Ayo, Abiodun
Pakos-Zebrucka, Karolina
Patterson, John B.
Logue, Susan E.
Samali, Afshin
Publication Date
2016-02-22
Type
Article
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Saveljeva, 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
Abstract
Upregulation 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.
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Impact Journals, LLC
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Attribution-NonCommercial-NoDerivs 3.0 Ireland