O-linked N-acetylgalactosamine modification is present on the tumor suppressor p53
2020
Xu, Zhijue | Ku, Xin | Tomioka, Azusa | Xie, Wenxian | Liang, Tao | Zou, Xia | Cui, Yalu | Satō, Takashi | Kaji, Hiroyuki | Narimatsu, Hisashi | Yan, Wei | Zhang, Yan
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.Using lectin blotting with GalNAc specific lectins, enzymatic treatments with O-GlcNAcase, core 1 β1, 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.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.These results revealed that the O-GalNAc glycosylation was a novel modification on p53.Our study provided a pilot evidence that the O-GalNAc glycosylation existed on nucleocytoplasmic protein.
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