Research Papers:

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

Yoon Kyung Jo, Na Yeon Park, So Jung Park, Byung-Gyu Kim, Ji Hyun Shin, Doo Sin Jo, Dong-Jun Bae, Young-Ah Suh, Jeong Ho Chang, Eun Kyung Lee, Sang-Yeob Kim, Jin Cheon Kim _ and Dong-Hyung Cho

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Oncotarget. 2016; 7:57186-57196. https://doi.org/10.18632/oncotarget.11083

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Yoon Kyung Jo1, Na Yeon Park1, So Jung Park1, Byung-Gyu Kim2, Ji Hyun Shin1, Doo Sin Jo1, Dong-Jun Bae3, Young-Ah Suh3, Jeong Ho Chang4, Eun Kyung Lee5, Sang-Yeob Kim3, Jin Cheon Kim3,6, Dong-Hyung Cho1

1Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea

2Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, School of Medicine, Kyungpook National University Hospital, Daegu, South Korea

3Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea

4Department of Biology Education, Kyungpook National University, Daegu, South Korea

5Department of Biochemistry, College of Medicine, Catholic University of Korea, Seoul, South Korea

6Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea

Correspondence to:

Jin Cheon Kim, email: jckim@amc.seoul.kr

Dong-Hyung Cho, email: dhcho@khu.ac.kr

Keywords: autophagy, ATG4B, O-GlcNAcylation, OGT, SH-SY5Y cells

Received: January 22, 2016     Accepted: July 26, 2016     Published: August 5, 2016


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.

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