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

• Published in: Oncotarget Vol. 7; no. 35; pp. 57186 - 57196
• Main Authors: Jo, Yoon Kyung, Park, Na Yeon, Park, So Jung, Kim, Byung-Gyu, Shin, Ji Hyun, Jo, Doo Sin, Bae, Dong-Jun, Suh, Young-Ah, Chang, Jeong Ho, Lee, Eun Kyung, Kim, Sang-Yeob, Kim, Jin Cheon, Cho, Dong-Hyung
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 30-08-2016
• Subjects: Acetylglucosamine - analogs & derivatives; Acetylglucosamine - metabolism; Animals; Autophagy; Autophagy-Related Proteins - chemistry; beta-N-Acetylhexosaminidases - metabolism; Cell Line, Tumor; Cysteine Endopeptidases - chemistry; Down-Regulation; Fibroblasts - metabolism; Fluorescent Dyes - chemistry; Gene Expression Regulation, Enzymologic; Glucose - chemistry; Humans; Immunoprecipitation; Luciferases - metabolism; Mass Spectrometry; Mice; Mixed Function Oxygenases - chemistry; N-Acetylglucosaminyltransferases - metabolism; Oximes - metabolism; Phenylcarbamates - metabolism; Research Paper; Signal Transduction; ATG4B; O-GlcNAcylation; autophagy; OGT; SH-SY5Y cells
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.11083

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.