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Deciphering Protein O-GalNAcylation: Method Development and Disease Implication
Shuang Yue1,2, Xiaotong Wang3,2, Wei Ge1
1Center for Clinical Mass Spectrometry, Department of Pharmaceutical Analysis, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
Abstract:
Mucin-type O-glycosylation is an important protein post-translational modification that is abundantly expressed on cell surface proteins. Protein O-glycosylation plays a variety of roles in cellular biological functions including protein structure and signal transduction to the immune response. Cell surface mucins are highly O-glycosylated and are the main substance of the mucosal barrier that protects the gastrointestinal or respiratory tract from infection by pathogens or microorganisms. Dysregulation of mucin O-glycosylation may impair mucosal protection against pathogens that can invade cells to trigger infection or immune evasion. Truncated O-glycosylation, also known as Tn antigen or O-GalNAcylation, is highly upregulated in diseases such cancer, autoimmune disorders, neurodegenerative diseases, and IgA nephropathy. Characterization of O-GalNAcylation helps decipher the role of Tn antigen in physiopathology and therapy. However, the analysis of O-glycosylation, specifically the Tn antigen, remains challenging due to the lack of reliable enrichment and identification assays compared to N-glycosylation. Here, we summarize recent advances in analytical methods for O-GalNAcylation enrichment and identification and highlight the biological role of the Tn antigen in various diseases and the clinical implications of identifying aberrant O-GalNAcylation.
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