Related Experiment Video

Updated: Sep 18, 2025

Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins
08:12

Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins

Published on: January 8, 2018

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ULK1-dependent phosphorylation of OGT instructs the tumorigenicity of O-GlcNAcylation

Zhuan Lv1, Qingen Da2, Yumiao Li3,4

  • 1Beijing Key Laboratory of DNA Damage Response and College of Life Sciences, Capital Normal University, Beijing, 100048, China.

Science China. Life Sciences
|June 26, 2025
PubMed

Insights

Glucose levels regulate O-linked N-acetylglucosamine (O-GlcNAc) by controlling O-GlcNAc transferase (OGT) stability. ULK1-mediated OGT phosphorylation at Ser576 under low glucose stabilizes OGT, promoting O-GlcNAc levels and tumorigenesis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • High O-linked N-acetylglucosamine (O-GlcNAc) levels are linked to various cancers.
  • The regulation of O-GlcNAc transferase (OGT) by nutrient availability, particularly glucose, is not well understood.
  • Understanding OGT's response to nutrients is crucial for cancer research.

Purpose of the Study:

  • To identify the mechanism by which OGT activity is regulated by glucose levels.
  • To investigate the role of unc-51 like autophagy activating kinase 1 (ULK1) in OGT regulation.
  • To explore the therapeutic potential of targeting OGT in cancer.

Main Methods:

  • Mass spectrometry to identify OGT phosphorylation sites.
  • Biochemical assays to study protein-protein interactions (OGT, ULK1, BAP1).
  • Generation and analysis of OGT Ser576 Alanine mutant (OGTS576A) knock-in cells in mouse xenograft models.

Main Results:

  • Glucose depletion induces OGT phosphorylation at Ser576 by ULK1, stabilizing OGT and increasing O-GlcNAcylation.
  • Phosphorylation at Ser576 inhibits OGT ubiquitination by promoting OGT-BAP1 interaction.
  • OGTS576A mutation abolished OGT tumorigenicity in mouse xenograft models, correlating with reduced O-GlcNAcylation.

Conclusions:

  • ULK1-mediated phosphorylation of OGT at Ser576 is a key regulatory mechanism under glucose deprivation.
  • This phosphorylation stabilizes OGT, enhances O-GlcNAcylation, and promotes tumorigenesis.
  • Targeting OGT phosphorylation presents a potential therapeutic strategy for glucose-associated cancers.
Keywords:
BAP1O-GlcNAcylationO-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT)ULK1glucose

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