Ogata, MaikoHino, Shin-ichiroSaito, AtsushiMorikawa, KeisukeKondo, ShinichiKanemoto, SoshiMurakami, TomohikoTaniguchi, ManabuTanii, IchiroYoshinaga, KazuyaShiosaka, SadaoHammarback, James A.Urano, FumihikoImaizumi, Kazunori2022-08-232022-08-232006-10-132011-04-19Mol Cell Biol. 2006 Dec;26(24):9220-31. Epub 2006 Oct 9. <a href="http://dx.doi.org/10.1128/MCB.01453-06">Link to article on publisher's site</a>0270-7306 (Linking)10.1128/MCB.01453-0617030611https://hdl.handle.net/20.500.14038/43902Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response, involving the induction of molecular chaperones, translational attenuation, and ER-associated degradation, to prevent cell death. Here, we found that the autophagy system is activated as a novel signaling pathway in response to ER stress. Treatment of SK-N-SH neuroblastoma cells with ER stressors markedly induced the formation of autophagosomes, which were recognized at the ultrastructural level. The formation of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 "dots"), representing autophagosomes, was extensively induced in cells exposed to ER stress with conversion from LC3-I to LC3-II. In IRE1-deficient cells or cells treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER stress was inhibited, indicating that the IRE1-JNK pathway is required for autophagy activation after ER stress. In contrast, PERK-deficient cells and ATF6 knockdown cells showed that autophagy was induced after ER stress in a manner similar to the wild-type cells. Disturbance of autophagy rendered cells vulnerable to ER stress, suggesting that autophagy plays important roles in cell survival after ER stress.en-USAutophagyCell Line, TumorCell SurvivalEndoplasmic ReticulumEnzyme ActivationHumansJNK Mitogen-Activated Protein KinasesProtein FoldingSignal TransductionStress, PhysiologicalTime FactorsGenetics and GenomicsJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1113&amp;context=pgfe_pp&amp;unstamped=1https://escholarship.umassmed.edu/pgfe_pp/1131946768pgfe_pp/113