O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity.

Autophagy is a catabolic degradation process and maintains cellular homeostasis. And autophagy is activated in response to various stress conditions. Although O-GlcNAcylation functions a sensor for nutrient and stress, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we identified that ATG4B is novel target for O-GlcNAcylation under metabolic ...
stress condition. Treatment with PugNAc, an O-GlcNAcase inhibitor increased activation of autophagy in SH-SY5Y cells. Both bimolecular fluorescence complementation and immunoprecipitation assay indicated that OGT directly interacts with ATG4B in SH-SY5Y cells. We also found that the O-GlcNAcylated ATG4B was increased in autophagy activation conditions, and down-regulation of OGT reduces O-GlcNAcylation of ATG4B under low glucose condition. Furthermore, the proteolytic activity of ATG4B for LC3 cleavage was enhanced in PugNAc-treated cells. Taken together, these results imply that O-GlcNAcylation of ATG4B regulates autophagy activation by increasing its proteolytic activity under metabolic stress condition.
Mesh Terms:
Acetylglucosamine, Animals, Autophagy, Autophagy-Related Proteins, Cell Line, Tumor, Cysteine Endopeptidases, Down-Regulation, Fibroblasts, Fluorescent Dyes, Gene Expression Regulation, Enzymologic, Glucose, Humans, Immunoprecipitation, Luciferases, Mass Spectrometry, Mice, Mixed Function Oxygenases, N-Acetylglucosaminyltransferases, Oximes, Phenylcarbamates, Signal Transduction, beta-N-Acetylhexosaminidases
Oncotarget
Date: Aug. 30, 2016
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