Laboratory of Glycobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
Cell Mol Biol Lett. 2024 Nov 7;29(1):137. doi: 10.1186/s11658-024-00658-7.
Human Gb3/CD77 synthase (α1,4-galactosyltransferase, P1/P 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.
人 Gb3/CD77 合酶（α1,4-半乳糖基转移酶，P1/P 合酶，UDP-半乳糖：β-D-半乳糖基-β1-R4-α-D-半乳糖基转移酶，EC 2.4.1.228）在糖脂和糖蛋白上形成 Galα1 → 4Gal 结构。这些聚糖被细菌黏附素和毒素识别。Gb3（三己糖酰基神经酰胺）是 Gb3/CD77 合酶的主要产物，是一种糖脂，主要位于质膜脂筏中，作为肠出血性大肠杆菌和志贺氏痢疾杆菌 1 型释放的志贺毒素的主要受体。另一方面，Gb3/CD77 合酶形成的聚糖积累导致α-半乳糖苷酶 A 缺乏引起的 Anderson-Fabry 病的症状。此外，Gb3/CD77 合酶表达和活性的变化是 P1PK 组织血型系统的基础。该酶合成的糖脂在结直肠癌、胃癌、胰腺癌和卵巢癌中过度产生，升高的 Gb3 生物合成与癌细胞化疗和放射抵抗有关。此外，Gb3/CD77 合酶作为一种关键的糖基转移酶，调节卵巢癌细胞的可塑性。在这里，我们描述了人 Gb3/CD77 合酶及其产物在 P1PK 组织血型系统、Anderson-Fabry 病和细菌感染中的作用。此外，我们还概述了新出现的证据，表明 Gb3/CD77 合酶及其糖脂产物参与了癌症转移和化疗耐药性。
