Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1863, Issue 5, Pages 870-882Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2019.01.009
Keywords
O-glycosylation; ppGaINAc-T18; GALNT18; ER stress; Non-catalytic
Categories
Funding
- National Science and Technology Major Project of China [2018ZX10302205]
- National Basic Research Program of China (973 Program) [2012CB822103]
- National High-tech R&D Program of China (863 Program) [2012AA020203]
- National Natural Science Foundation of China [31370806, 31170771, 31570796, 31770850]
- International Science & Technology Cooperation Program of China [2012DFG32190]
- Specialized Research Fund for the Doctoral Program of Higher Education Grant [20130073110088]
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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.
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