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Oncotarget. 2016 Aug 30;7(35):57186-57196. doi: 10.18632/oncotarget.11083.

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

Author information

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.

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

PMID:
27527864
PMCID:
PMC5302982
DOI:
10.18632/oncotarget.11083
[Indexed for MEDLINE]
Free PMC Article

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