C1GALT1 in health and disease (Review)

Abstract

O-linked glycosylation ( O -glycosylation) and N-linked glycosylation ( N -glycosylation) are the two most important forms of protein glycosylation, which is an important post-translational modification. The regulation of protein function involves numerous mechanisms, among which protein glycosylation is one of the most important. Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 ( C1GALT1 ) serves an important role in the regulation of O -glycosylation and is an essential enzyme for synthesizing the core 1 structure of mucin-type O-glycans. Furthermore, C1GALT1 serves a vital role in a number of biological functions, such as angiogenesis, platelet production and kidney development. Impaired C1GALT1 expression activity has been associated with different types of human diseases, including inflammatory or immune-mediated diseases, and cancer. O -glycosylation exists in normal tissues, as well as in tumor tissues. Previous studies have revealed that changes in the level of glycosyltransferase in different types of cancer may be used as potential therapeutic targets. Currently, numerous studies have reported the dual role of C1GALT1 in tumors (carcinogenesis and cancer suppression). The present review reports the role of C1GALT1 in normal development and human diseases. Since the mechanism and regulation of C1GALT1 and O -glycosylation remain elusive, further studies are required to elucidate their effects on development and disease.

Finding the sweet spot: glycosylation mediated regulation of intestinal inflammation

“…The initial O-glycan structure linked to Ser or Thr, referred to as Thomsen-nouveau (Tn) antigen (GalNAca-O-Ser/Thr), is subsequently extended by additional monosaccharides transferred to growing glycan chains by specific glycosyltransferases. A ubiquitously expressed glycosyltransferase (Core 1 β1-3-galactosyltransferase, C1GalT1) adds Gal to Tn structures forming Core 1 type O-glycans (Galβ1-3GalNAc) 8 , 9 . An additional glycosyltransferase, Core 3 β1-3-N-Acetylglucosaminyltransferase (C3GnT), adds GlcNAc to Tn structures to form core 3 derived O-glycans 10 , 11 (Fig.…”

Exposure of Keratinocytes to Candida Albicans in the Context of Atopic Milieu Induces Changes in the Surface Glycosylation Pattern of Small Extracellular Vesicles to Enhance Their Propensity to Interact With Inhibitory Siglec Receptors

“…ST6GAL1 was also recently shown as enzymatically active cargo of both exosome-like sEVs and exomeres, capable of transferring sialyltransferase activity to receipient cells and inducing expression of sialylated proteins on the cell membrane (67). As for the C1GALT1 enzyme, it has also been implicated in cancer; however, the role is less clear-cut, with contradicting data on the pro-/antitumorogenic effect (68). The enzyme has also been linked to IgA nephropathy by deposition of galactose-deficient IgA1 (Gd-IgA1) circulating in the patients with C1GALT1 mutation (69).…”

A Sweet Warning: Mucin-Type O-Glycans in Cancer

“…The importance of glycosylation in various physiological and pathological processes, and in the development of biopharmaceuticals over the past decade cannot be overstated [ 29 ]. Normal biosynthesis of mucin-type O-glycans is associated with body health and internal environmental homeostasis, whereas abnormal mucin-type O-glycans are related to the development of cancer and other pathological processes [ 30 ]. More than 100 rare congenital disorders of glycosylation (CDG) are caused by defects in genes that regulate glycosylation, 50 of which are caused by defects in the glycosyltransferase genes [ 31 ].…”