期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1864, 期 8, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbagen.2020.129635
关键词
O-GalNAc glycosylation; p53; Nucleocytoplasmic protein; UDP-Gal/UDP-GalNAc 4-epimerase; GalNAz-metabolic labeling
资金
- National Science and Technology Major Project of China [2018ZX10302205]
- National Basic Research Program of China (973 Program) [2012CB822103]
- National Hightech R&D Program of China (863 Program) [2012AA020203]
- National Natural Science Foundation of China [31170771, 31370806, 31570796, 31770850]
- Chinese Postdoctoral Science Foundation [2018M642004]
Background: Mucin-type O-glycosylation (referred to as O-GalNAc glycosylation) is the most abundant O-glycosylation on membrane and secretory proteins. Recently several evidences suggest that nuclear or cytoplasmic proteins might also have O-GalNAc glycosylation. However, what nucleocytoplasmic proteins are O-GalNAc glycosylated and what the biological function of this modification in cells are still poorly understood. Previously, we reported the tumor suppressor p53 could be O-GalNAc glycosylated in vitro. To investigate the existence and function of O-GalNAc glycosylation on nucleocytoplasmic proteins in cell, p53 as a representative nucleocytoplasmic protein was studied. Methods: Using lectin blotting with GalNAc specific lectins, enzymatic treatments with O-GlcNAcase, core 1 beta 1, 3-galactosyltransferase and O-glycosidase, and metabolic labeling with un-O-acetylated GalNAz in UDP-Gal/UDP-GalNAc 4-epimerase (GALE) knockout cells, we validated the O-GalNAc glycosylation on p53. Using mass spectrometry analysis and site-directed mutagenesis, we identified the glycosylated sites and studied the functions of O-GalNAc glycosylation on p53. Results: The p53 was O-GalNAc glycosylated in cells. Ser121 residue was one of the glycosylated sites on p53. The O-GalNAc glycosylation at Ser121 was associated with the stability and activity of p53. Conclusions: These results revealed that the O-GalNAc glycosylation was a novel modification on p53. General significance: Our study provided a pilot evidence that the O-GalNAc glycosylation existed on nucleocytoplasmic protein.
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