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O-GlcNAcylation of eIF2α regulates the phospho-eIF2α-mediated ER stress response.

DC FieldValueLanguage
dc.contributor.author김재우-
dc.contributor.author조진원-
dc.contributor.author최현진-
dc.date.accessioned2016-02-04T11:32:30Z-
dc.date.available2016-02-04T11:32:30Z-
dc.date.issued2015-
dc.identifier.issn0167-4889-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/140657-
dc.description.abstractO-GlcNAcylation is highly involved in cellular stress responses including the endoplasmic reticulum (ER) stress response. For example, glucosamine-induced flux through the hexosamine biosynthetic pathway can promote ER stress and ER stress inducers can change the total cellular level of O-GlcNAcylation. However, it is largely unknown which component(s) of the unfolded protein response (UPR) is directly regulated by O-GlcNAcylation. In this study, eukaryotic translation initiation factor 2α (eIF2α), a major branch of the UPR, was O-GlcNAcylated at Ser 219, Thr 239, and Thr 241. Upon ER stress, eIF2α is phosphorylated at Ser 51 by phosphorylated PKR-like ER kinase and this inhibits global translation initiation, except for that of specific mRNAs, including activating transcription factor 4, that induce stress-responsive genes such as C/EBP homologous protein (CHOP). Hyper-O-GlcNAcylation induced by O-GlcNAcase inhibitor (thiamet-G) treatment or O-GlcNAc transferase (OGT) overexpression hindered phosphorylation of eIF2α at Ser 51. The level of O-GlcNAcylation of eIF2α was changed by dithiothreitol treatment dependent on its phosphorylation at Ser 51. Point mutation of the O-GlcNAcylation sites of eIF2α increased its phosphorylation at Ser 51 and CHOP expression and resulted in increased apoptosis upon ER stress. These results suggest that O-GlcNAcylation of eIF2α affects its phosphorylation at Ser 51 and influences CHOP-mediated cell death. This O-GlcNAcylation of eIF2α was reproduced in thiamet-G-injected mouse liver. In conclusion, proper regulation of O-GlcNAcylation and phosphorylation of eIF2α is important to maintain cellular homeostasis upon ER stress.-
dc.description.statementOfResponsibilityopen-
dc.format.extent1860~1869-
dc.relation.isPartOfBiochimica et Biophysica Acta - Molecular Cell Research-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleO-GlcNAcylation of eIF2α regulates the phospho-eIF2α-mediated ER stress response.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Biochemistry & Molecular Biology (생화학,분자생물학)-
dc.contributor.googleauthorInsook Jang-
dc.contributor.googleauthorHan Byeol Kim-
dc.contributor.googleauthorHojoong Seo-
dc.contributor.googleauthorJin Young Kim-
dc.contributor.googleauthorHyeonjin Choi-
dc.contributor.googleauthorJong Shin Yoo-
dc.contributor.googleauthorJae-woo Kim-
dc.contributor.googleauthorJin Won Cho-
dc.identifier.doi10.1016/j.bbamcr.2015.04.017-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00865-
dc.relation.journalcodeJ00291-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0167488915001366-
dc.contributor.alternativeNameKim, Jae Woo-
dc.contributor.alternativeNameCho, Jin Won-
dc.contributor.alternativeNameChoi, Hyeonjin-
dc.contributor.affiliatedAuthorKim, Jae Woo-
dc.rights.accessRightsnot free-
dc.citation.volume1853-
dc.citation.number8-
dc.citation.startPage1860-
dc.citation.endPage1869-
dc.identifier.bibliographicCitationBiochimica et Biophysica Acta - Molecular Cell Research, Vol.1853(8) : 1860-1869, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers

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