O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity
- Oncotarget. 2016 Aug 30;7(35):57186-57196. doi: 10.18632/oncotarget.11083.
- 1. Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
- 2. Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, School of Medicine, Kyungpook National University Hospital, Daegu, South Korea.
- 3. Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
- 4. Department of Biology Education, Kyungpook National University, Daegu, South Korea.
- 5. Department of Biochemistry, College of Medicine, Catholic University of Korea, Seoul, South Korea.
- 6. Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
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.