TY - CHAP

T1 - Mucin-Type O-GalNAc Glycosylation in Health and Disease

AU - Bagdonaite, Ieva

AU - Pallesen, Emil M.H.

AU - Nielsen, Mathias I.

AU - Bennett, Eric P.

AU - Wandall, Hans H.

N1 - Publisher Copyright: © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.

PY - 2021

Y1 - 2021

N2 - Mucin-type GalNAc O-glycosylation is one of the most abundant and unique post-translational modifications. The combination of proteome-wide mapping of GalNAc O-glycosylation sites and genetic studies with knockout animals and genome-wide analyses in humans have been instrumental in our understanding of GalNAc O-glycosylation. Combined, such studies have revealed well-defined functions of O-glycans at single sites in proteins, including the regulation of pro-protein processing and proteolytic cleavage, as well as modulation of receptor functions and ligand binding. In addition to isolated O-glycans, multiple clustered O-glycans have an important function in mammalian biology by providing structural support and stability of mucins essential for protecting our inner epithelial surfaces, especially in the airways and gastrointestinal tract. Here the many O-glycans also provide binding sites for both endogenous and pathogen-derived carbohydrate-binding proteins regulating critical developmental programs and helping maintain epithelial homeostasis with commensal organisms. Finally, O-glycan changes have been identified in several diseases, most notably in cancer and inflammation, where the disease-specific changes can be used for glycan-targeted therapies. This chapter will review the biosynthesis, the biology, and the translational perspectives of GalNAc O-glycans.

AB - Mucin-type GalNAc O-glycosylation is one of the most abundant and unique post-translational modifications. The combination of proteome-wide mapping of GalNAc O-glycosylation sites and genetic studies with knockout animals and genome-wide analyses in humans have been instrumental in our understanding of GalNAc O-glycosylation. Combined, such studies have revealed well-defined functions of O-glycans at single sites in proteins, including the regulation of pro-protein processing and proteolytic cleavage, as well as modulation of receptor functions and ligand binding. In addition to isolated O-glycans, multiple clustered O-glycans have an important function in mammalian biology by providing structural support and stability of mucins essential for protecting our inner epithelial surfaces, especially in the airways and gastrointestinal tract. Here the many O-glycans also provide binding sites for both endogenous and pathogen-derived carbohydrate-binding proteins regulating critical developmental programs and helping maintain epithelial homeostasis with commensal organisms. Finally, O-glycan changes have been identified in several diseases, most notably in cancer and inflammation, where the disease-specific changes can be used for glycan-targeted therapies. This chapter will review the biosynthesis, the biology, and the translational perspectives of GalNAc O-glycans.

KW - Cancer

KW - Carbohydrate-binding proteins

KW - GalNAc

KW - Glycans

KW - Mucins

KW - Proprotein processing

U2 - 10.1007/978-3-030-70115-4_2

DO - 10.1007/978-3-030-70115-4_2

M3 - Book chapter

C2 - 34495529

AN - SCOPUS:85115023395

SN - 978-3-030-70117-8

T3 - Advances in Experimental Medicine and Biology

SP - 25

EP - 60

BT - The Role of Glycosylation in Health and Disease

PB - Springer VS

ER -