2. Academic Validation
  3. O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity

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.
Yoon Kyung Jo 1,  Na Yeon Park 1,  So Jung Park 1,  Byung-Gyu Kim 2,  Ji Hyun Shin 1,  Doo Sin Jo 1,  Dong-Jun Bae 3,  Young-Ah Suh 3,  Jeong Ho Chang 4,  Eun Kyung Lee 5,  Sang-Yeob Kim 3,  Jin Cheon Kim 3 6,  Dong-Hyung Cho 1
Affiliations

Affiliations

  • 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.
PMID: 27527864 DOI: 10.18632/oncotarget.11083
Abstract

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.

Keywords

ATG4B; O-GlcNAcylation; OGT; SH-SY5Y cells; autophagy.

Figures