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Human Gb3/CD77 synthase: a glycosyltransferase at the crossroads of immunohematology, toxicology, and cancer research.

Authors :
Szymczak-Kulus, Katarzyna
Czerwinski, Marcin
Kaczmarek, Radoslaw
Source :
Cellular & Molecular Biology Letters; 11/7/2024, Vol. 29 Issue 1, p1-16, 16p
Publication Year :
2024

Abstract

Human Gb3/CD77 synthase (α1,4-galactosyltransferase, P1/P<superscript>k</superscript> synthase, UDP-galactose: β-d-galactosyl-β1-R 4-α-d-galactosyltransferase, EC 2.4.1.228) forms Galα1 → 4Gal structures on glycosphingolipids and glycoproteins. These glycans are recognized by bacterial adhesins and toxins. Globotriaosylceramide (Gb3), the major product of Gb3/CD77 synthase, is a glycosphingolipid located predominantly in plasma membrane lipid rafts, where it serves as a main receptor for Shiga toxins released by enterohemorrhagic Escherichia coli and Shigella dysenteriae of serotype 1. On the other hand, accumulation of glycans formed by Gb3/CD77 synthase contributes to the symptoms of Anderson–Fabry disease caused by α-galactosidase A deficiency. Moreover, variation in Gb3/CD77 synthase expression and activity underlies the P1PK histo-blood group system. Glycosphingolipids synthesized by the enzyme are overproduced in colorectal, gastric, pancreatic, and ovarian cancer, and elevated Gb3 biosynthesis is associated with cancer cell chemo- and radioresistance. Furthermore, Gb3/CD77 synthase acts as a key glycosyltransferase modulating ovarian cancer cell plasticity. Here, we describe the role of human Gb3/CD77 synthase and its products in the P1PK histo-blood group system, Anderson–Fabry disease, and bacterial infections. Additionally, we provide an overview of emerging evidence that Gb3/CD77 synthase and its glycosphingolipid products are involved in cancer metastasis and chemoresistance. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14258153
Volume :
29
Issue :
1
Database :
Complementary Index
Journal :
Cellular & Molecular Biology Letters
Publication Type :
Academic Journal
Accession number :
180735453
Full Text :
https://doi.org/10.1186/s11658-024-00658-7