Cosmc和T-合酶在黏蛋白型O-聚糖合成中的重要作用及其与人类疾病的相关性

从核心1结构（Galβ1,3GalNAcα1-O-Ser/Thr, core 1 structure, T antigen）中衍生出来的黏蛋白型O-聚糖在很多生理过程中发挥重要的生物学功能。T-合酶 （core 1 β3-galactosyltransferase, T-synthase） 是合成核心1结构的唯一糖基转移酶，它主要的功能是将半乳糖（Galactose） 添加到GalNAcα1-Ser/Thr （Tn抗原） 糖链上。但是在人体和其他脊椎动物中有活性的T-合酶的形成需要一个重要的伴侣分子Cosmc；Cosmc功能丧失将直接导致T-合酶失活，其结果是机体细胞只能合成Tn抗原以及唾液酰化Tn （sialylTn, STn, Neu5Acα2,6GalNAcα1-O-Ser/Thr）。综述目前对T-合酶和Cosmc的研究以及他们在人类疾病（如异常O-聚糖表达相关的Tn综合征、IgA肾病和肿瘤）发生发展中的作用。

The key role of Cosmc and T-synthase in mucin-type O-glycan biosynthesisimplications in human diseases

Mucin type O-glycans, primarily derived from the core 1 structure, play pivotal functions in many biological processes. The T-synthase （core 1 [33-galactosyltransferase） is the key enzyme responsible for synthesizing the core l O-glycan GalD 1,3GalNAcctl-Ser/Thr （T antigen） through addition of Gal to GalNAcct 1-Ser/ Thr （Tn antigen）. Interestingly, formation of active T-synthase in human and other vertebrates requires a specific molecular chaperone, Cosmc. Dysfunction of Cosmc results in an inactive T-synthase leading to expression of the Tn antigen and its sialylated version, sialylTn （STn, Neu5Acct2,6GalNAcul-Ser/Thr）. This review summarizes the current understanding of the T-synthase and Cosmc regarding their biochemistry and biology, as well as their roles in human diseases, such as Tn syndrome, IgA nephropathy, and human tumors, which are associated with expression of abnormal O-glycans.