ULK1 O-GlcNAcylation Is Crucial for Activating VPS34 via ATG14L during Autophagy Initiationopen access
- Authors
- Pyo, Ki Eun; Kim, Chang Rok; Lee, Minkyoung; Kim, Jong-Seo; Kim, Keun Il; Baek, Sung Hee
- Issue Date
- Dec-2018
- Publisher
- CELL PRESS
- Keywords
- AMPK; autophagy initiation; mTORC1; O-GlcNACylation; phagophore formation; PP1; ULK1
- Citation
- CELL REPORTS, v.25, no.10, pp 2878 - +
- Journal Title
- CELL REPORTS
- Volume
- 25
- Number
- 10
- Start Page
- 2878
- End Page
- +
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/4149
- DOI
- 10.1016/j.celrep.2018.11.042
- ISSN
- 2211-1247
- Abstract
- Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation. Upon glucose starvation, dissociation of mTOR from ULK1 and phosphorylation by AMPK leads to the activation of ULK1 activity. Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation. ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK. ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3) P), which is required for phagophore formation and initiation of autophagy. Our findings provide insights into the crosstalk between dephosphorylation and O-GlcNAcylation during autophagy and specify a molecular framework for potential therapeutic intervention in autophagy-related diseases.
- Files in This Item
-
Go to Link
- Appears in
Collections - 이과대학 > 생명시스템학부 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.