Polypeptide N-acetylgalactosaminyltransferase 18 non-catalytically regulates the ER homeostasis and O-glycosylation
| Autor: | Yan Zhang, Yingjiao Xu, Feng Liu, Xing Li, Fang Yang, Aidong Shan, Takashi Sato, Zhijue Xu, Jishun Lu, Wei Li, Hisashi Narimatsu |
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| Rok vydání: | 2019 |
| Předmět: |
Glycosylation
Biophysics Polypeptide N-acetylgalactosaminyltransferase Endoplasmic Reticulum PC12 Cells Biochemistry 03 medical and health sciences chemistry.chemical_compound symbols.namesake 0302 clinical medicine Animals Homeostasis Humans Gene silencing Molecular Biology 030304 developmental biology 0303 health sciences Gene knockdown Endoplasmic reticulum Golgi apparatus Rats Cell biology carbohydrates (lipids) HEK293 Cells chemistry A549 Cells 030220 oncology & carcinogenesis symbols Unfolded protein response N-Acetylgalactosaminyltransferases Chemical chaperone |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - General Subjects. 1863:870-882 |
| ISSN: | 0304-4165 |
| Popis: | Mucin-type O-glycosylation plays important roles in various biological processes. It is initiated by a family of 20 conserved UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts). Unlike most ppGalNAc-Ts localized to the Golgi apparatus, ppGalNAc-T18 is predominantly distributed on the endoplasmic reticulum (ER) and exhibits no ppGalNAc-T catalytic activity in vitro. Herein, we found that ppGalNAc-T18 silencing in cells decreased O-glycosylation levels and activated ER stress leading to apoptosis. After treatment with chemical chaperone 4-phenylbutyric acid (PBA) or forced expression of ppGalNAc-T18 in the ppGalNAc-T18 knockdown cell, these defects could be significantly alleviated, suggesting that ppGalNAc-T18 is important for ER homeostasis and protein O-glycosylation. Furthermore, we found that ppGalNAc-T18 exerts its functions in O-glycosylation and ER stress via a non-catalytic mechanism. These results reveal a novel molecular role of ppGalNAc-Ts that the ER-localized ppGalNAc-T18 could regulate the O-glycosylation and ER homeostasis in a non-catalytic manner. |
| Databáze: | OpenAIRE |
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