《生命科学》 2018, 30(11): 1264-1274

疾病及发育中多肽：N-乙酰氨基半乳糖转移酶ppGalNAc-T的重要性

崔雅璐，徐颖姣，贾文娟，杨　芳，张　延*

(上海交通大学系统生物医学研究院，系统生物医学教育部重点实验室，上海 200240)

摘　要：摘　要：蛋白质的O-GalNAc 糖基化是生物体内广泛存在的一种重要的蛋白质翻译后修饰，参与了众多生命活动过程。多肽：N- 乙酰氨基半乳糖转移酶(ppGalNAc-T 酶) 是调控蛋白质O-GalNAc 糖基化修饰的起始糖基转移酶，它催化N- 乙酰氨基半乳糖(GalNAc) 共价结合到蛋白质丝氨酸或苏氨酸的侧链羟基上，形成Tn 糖链抗原结构。人体内ppGalNAc-T 酶家族共有20 个成员，各成员在不同的组织和细胞中的表达具有时空特异性，同时对其修饰的底物蛋白存在选择性。ppGalNAc-T 酶的异常表达与组织器官发育，以及肿瘤、家族性钙质沉积、冠心病、阿尔兹海默症、先天性心脏病等复杂性疾病的发生发展密切相关。该文总结了近年来关于ppGalNAc-T 酶在组织器官发育过程以及复杂性疾病发生发展中的研究概况，为深入理解ppGalNAc-T 酶和O- 糖基化的功能及其生物学意义提供参考。

The importance of polypeptide N-acetylgalactosaminyltransferases in diseases and development

CUI Ya-Lu， XU Ying-Jiao， JIA Wen-Juan， YANG Fang， ZHANG Yan*

(Key Laboratory of Systems Biomedicine (Ministry of Education)， Shanghai Center for Systems Biomedicine， Shanghai Jiao Tong University， Shanghai 200240， China)

Abstract: Abstract: Mucin-type O-glycosylation (refer O-GalNAc glycosylation) is an important post-modification of protein involved in various biological processes. It is initiated by a group of UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferases，which transfer the GalNAc residue to the side-chain hydroxyl group on Ser or Thr of target proteins to form the Tn antigens. ppGalNAc-Ts include 20 members in human. Each isoform of ppGalNAc-Ts displays
    tissue-specific expression in adult mammals with substrate specificity and unique spatial as well as temporal pattern of expression during murine development. In the past decade， increasing evidence has demonstrated that aberrant expression of ppGalNAc-Ts is tightly associated with the complex diseases such as familial tumoral calcinosis， coronary heart disease， Alzheimer's disease， congenital heart disease and the progression of various cancers as well.Here， we summarize the research overview of the expression of different ppGalNAc-Ts in normal development and these diseases， describe the functional and molecular effects of their disregulation and discuss potential molecular mechanisms underlying these processes.