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.
Pubmed ID: 30517873 RIS Download
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This polyclonal targets Human FRAP1
View all literature mentionsThis unknown targets Atg1 / ULK1
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal targets ATG101 antibody
View all literature mentionsThis monoclonal targets O-Linked N-Acetylglucosamine
View all literature mentionsThis polyclonal targets ATG13 antibody produced in rabbit
View all literature mentionsThis monoclonal targets Phosphoserine
View all literature mentionsThis polyclonal targets OGT / O-Linked N-Acetylglucosamine Transferase antibody
View all literature mentionsThis polyclonal targets Beclin 1
View all literature mentionsThis monoclonal targets HA.11
View all literature mentionsThis monoclonal targets HA.11
View all literature mentionsThis polyclonal targets OGT / O-Linked N-Acetylglucosamine Transferase antibody
View all literature mentionsThis monoclonal targets O-Linked N-Acetylglucosamine
View all literature mentionsThis polyclonal targets ATG101 antibody
View all literature mentionsThis polyclonal targets Human FRAP1
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets Phosphoserine
View all literature mentionsThis polyclonal targets ATG13 antibody produced in rabbit
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets Atg1 / ULK1
View all literature mentionsThis polyclonal targets Beclin 1
View all literature mentions