Department of Glyco-Oncology and Medical Biochemistry, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan.
Biochem Soc Trans. 2021 Feb 26;49(1):441-453. doi: 10.1042/BST20200780.
Glycosylation represents one of the most abundant posttranslational modification of proteins. Glycosylation products are diverse and are regulated by the cooperative action of various glycosyltransferases, glycosidases, substrates thereof: nucleoside sugars and their transporters, and chaperons. In this article, we focus on a glycosyltransferase, α1,6-fucosyltransferase (Fut8) and its product, the core fucose structure on N-glycans, and summarize the potential protective functions of this structure against emphysema and chronic obstructive pulmonary disease (COPD). Studies of FUT8 and its enzymatic product, core fucose, are becoming an emerging area of interest in various fields of research including inflammation, cancer and therapeutics. This article discusses what we can learn from studies of Fut8 and core fucose by using knockout mice or in vitro studies that were conducted by our group as well as other groups. We also include a discussion of the potential protective functions of the keratan sulfate (KS) disaccharide, namely L4, against emphysema and COPD as a glycomimetic. Glycomimetics using glycan analogs is one of the more promising therapeutics that compensate for the usual therapeutic strategy that involves targeting the genome and the proteome. These typical glycans using KS derivatives as glycomimetics, will likely become a clue to the development of novel and effective therapeutic strategies.
糖基化是蛋白质最丰富的翻译后修饰之一。糖基化产物多种多样,受各种糖基转移酶、糖苷酶、其底物:核苷糖及其转运蛋白和伴侣的协同作用调节。在本文中,我们专注于一种糖基转移酶,α1,6-岩藻糖基转移酶(Fut8)及其产物,N-糖聚糖上的核心岩藻糖结构,并总结了该结构对肺气肿和慢性阻塞性肺疾病(COPD)的潜在保护作用。FUT8 及其酶产物核心岩藻糖的研究正在成为包括炎症、癌症和治疗学在内的各个研究领域的一个新兴兴趣领域。本文讨论了我们可以从 Fut8 和核心岩藻糖的研究中学习到什么,这些研究使用了我们小组以及其他小组进行的基因敲除小鼠或体外研究。我们还讨论了角蛋白硫酸盐 (KS) 二糖即 L4 对肺气肿和 COPD 的潜在保护作用,作为糖模拟物。使用聚糖类似物的糖模拟物是更有前途的治疗方法之一,它可以弥补通常的靶向基因组和蛋白质组的治疗策略。这些使用 KS 衍生物作为糖模拟物的典型聚糖可能成为开发新型有效治疗策略的线索。