Unknown

Dataset Information

0

Endoplasmic reticulum stress-mediated induction of SESTRIN 2 potentiates cell survival.


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?, 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.

SUBMITTER: Saveljeva S 

PROVIDER: S-EPMC4914282 | BioStudies | 2016-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC5528439 | BioStudies
2016-01-01 | S-EPMC5115827 | BioStudies
2019-01-01 | S-EPMC6692737 | BioStudies
2020-01-01 | S-EPMC7156099 | BioStudies
2013-01-01 | S-EPMC3869453 | BioStudies
2019-01-01 | S-EPMC6678695 | BioStudies
1000-01-01 | S-EPMC6158215 | BioStudies
2018-01-01 | S-EPMC6245652 | BioStudies
2019-01-01 | S-EPMC6660483 | BioStudies
2017-01-01 | S-EPMC5564770 | BioStudies