The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu city, Gifu 501-1193, Japan.
Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu city, Gifu 501-1193, Japan.
Biochim Biophys Acta Gen Subj. 2024 Nov;1868(11):130709. doi: 10.1016/j.bbagen.2024.130709. Epub 2024 Sep 2.
The β1,6-GlcNAc branch in N-glycans, produced by a glycosyltransferase N-acetylglucosaminyltransferase V (GnT-V or MGAT5), is associated with cancer and autoimmune diseases.
Here, we summarize the structure and activity regulation of GnT-V. We also describe the roles of the β1,6-GlcNAc branch on glycoproteins in cells and the phenotypes of Mgat5-deficient mice, focusing on cancer and the immune system.
GnT-V has a unique structure for substrate recognition, and its activity and function are regulated by shedding. The glycans produced by GnT-V play pivotal roles in the differentiation of neural cells, cancer malignancy and immunotherapy, and the development of autoimmune diseases by regulating the functions and cell surface residency of glycoproteins.
Controlling the expression or activity of GnT-V could be a therapeutic option against cancer and autoimmune diseases. Future work should clarify how GnT-V selectively modifies the specific glycoproteins or N-glycosylation sites in vivo.
N-糖基化中β1,6-GlcNAc 分支由糖基转移酶 N-乙酰氨基葡萄糖转移酶 V（GnT-V 或 MGAT5）产生，与癌症和自身免疫性疾病有关。
本文总结了 GnT-V 的结构和活性调节。我们还描述了糖蛋白上 β1,6-GlcNAc 分支在细胞中的作用以及 Mgat5 缺陷型小鼠的表型，重点关注癌症和免疫系统。
GnT-V 具有独特的底物识别结构，其活性和功能受脱落调节。由 GnT-V 产生的聚糖在神经细胞分化、癌症恶性程度和免疫治疗以及自身免疫性疾病的发展中通过调节糖蛋白的功能和细胞表面驻留发挥关键作用。
控制 GnT-V 的表达或活性可能是治疗癌症和自身免疫性疾病的一种选择。未来的工作应该阐明 GnT-V 如何在体内选择性修饰特定的糖蛋白或 N-糖基化位点。
