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Functional Study of O-GlcNAcylation on ULK1 under glucose deprivation

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dc.contributor.authorPak, Jin Won-
dc.date.accessioned2017-07-11T16:10:20Z-
dc.date.available2017-07-11T16:10:20Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/149127-
dc.descriptionDept. of Integrated OMICS for Biomedical Science,/박사-
dc.description.abstractO-GlcNAcylation is a dynamic posttranslational modification that occurs in the serine or threonine residues of nuclear and cytosolic proteins. O-GlcNAcylation regulates various cellular events, such as a nutrient sensing, epigenetic regulation, translational regulation, and cell proliferation, as well as disease-related signal pathways. UDP-GlcNAc, a precursor of O-GlcNAcylation, is synthesized from glucose by the hexosamine biosynthetic pathway (HBP). The level of UDP-GlcNAc depends on the cellular glucose condition. For this reason, O-GlcNAcylation is called a nutrient sensor. Although O-GlcNAcylation plays a role in nutrient sensing and metabolism, the relationship between O-GlcNAcylation and autophagy remains unknown. In previous studies, decreased O-GlcNAcylation by OGT siRNA induced autophagy without starvation. In this study, we observed that a unc-51 like autophagy activating kinase 1(ULK1), a regulator of autophagy, is O-GlcNAcylated. Under glucose deprivation, O-GlcNAcylated ULk1 is increased, and increased O-GlcNAcylation induces ULK1 S757 phosphorylation, which leads to ULK1 inactivation. The ULK1 S757A mutant decreases O-GlcNAcylation on ULK1 and binding affinity with OGT compared with ULK1 wild type. These data imply that O-GlcNAcylation on ULK1 decreases ULK1 kinase activity by increasing S757 phosphorylation and reduces autophagy induction.-
dc.description.statementOfResponsibilityopen-
dc.publisherGraduate School, Yonsei University-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleFunctional Study of O-GlcNAcylation on ULK1 under glucose deprivation-
dc.title.alternative포도당 결핍상태에서 ULK1의 O-GlcNAc 수식화 기능연구-
dc.typeThesis-
dc.contributor.alternativeNamePak, Jin Won-
dc.type.localDissertation-
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 3. Dissertation

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