Peer-Reviewed Journal Details
Mandatory Fields
Saveljeva, S,Cleary, P,Mnich, K,Ayo, A,Pakos-Zebrucka, K,Patterson, JB,Logue, SE,Samali, A
2016
March
Oncotarget
Endoplasmic reticulum stress-mediated induction of SESTRIN 2 potentiates cell survival
Published
()
Optional Fields
SESTRIN 2 ER stress UPR cell death autophagy UNFOLDED PROTEIN RESPONSE ER-STRESS TRANSCRIPTIONAL REGULATION PERK AUTOPHAGY DEATH CARCINOMA APOPTOSIS
7
12254
12266
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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