title: O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity.
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.
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jo
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Na Yeon
authors.initials: NY
authors.lastname: Park
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, School of Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Byung-Gyu
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Doo Sin
authors.initials: DS
authors.lastname: Jo
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Bae
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Suh
authors.affiliation: Department of Biology Education, Kyungpook National University, Daegu, South Korea.
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Biochemistry, College of Medicine, Catholic University of Korea, Seoul, South Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.|Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000737:chemistry; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D006899:Mixed Function Oxygenases / Q000737:chemistry*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D010091:Oximes / Q000378:metabolism; D048448:Phenylcarbamates / Q000378:metabolism; D015398:Signal Transduction; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D000071183:Autophagy-Related Proteins; D005456:Fluorescent Dyes; D010091:Oximes; D048448:Phenylcarbamates; C068836:N-acetylglucosaminono-1,5-lactone O-(phenylcarbamoyl)oxime; D006899:Mixed Function Oxygenases; D008156:Luciferases; D017351:N-Acetylglucosaminyltransferases; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; C507524:ATG4B protein, human; D003546:Cysteine Endopeptidases; D005947:Glucose; D000117:Acetylglucosamine
keywords: ATG4B; O-GlcNAcylation; OGT; SH-SY5Y cells; autophagy