摘要
O-GlcNAc是一种广泛存在于蛋白质丝/苏氨酸残基上的动态可逆的蛋白质翻译后修饰方式,广泛分布在细胞浆和细胞核中,参与调节多种细胞途径。蛋白质的O-GlcNAc糖基化与许多疾病密切相关,如糖尿病、神经退行性疾病和癌症等。在体内,O-GlcNAc动态修饰由N-乙酰氨基葡萄糖转移酶(OGT)和N-乙酰氨基葡萄糖苷酶(OGA)协同完成。OGT具有3种异构体,分别是ncOGT、mOGT和sOGT。目前对于mOGT的功能和调节机制尚未清楚。作者在酿酒酵母细胞中表达了人源的mOGT,发现mOGT抑制酵母细胞的生长。在酿酒酵母细胞中mOGT具有O-GlcNAc糖基化活性,当其活性位点突变后,O-GlcNAc糖基化活性明显降低,但其同样能抑制酵母细胞生长。作者在酿酒酵母细胞中构建了研究mOGT的系统。可以利用该人源化的酵母筛选和mOGT相互作用的蛋白质和基因,也可以用来筛选抑制mOGT活性的药物,进而研究mOGT的功能与调节机制。
N-acetylglucosamine （O-GlcNAc） modification on protein serines/threonines is a dynamic,inducible and abundant post-translational modification,which is found on numerous cytoplasm and nucleus proteins,regulating many cellular process. I t has demonstrated that O-GlcNAc plays important roles in some human diseases, such as diabetes and neurodegenerative. O-GlcNAcylation cycle is regulated by O-GlcNAc transferase （OGT） and O-GlcNAcase （OGA） in vivo. There are three isoforms of OGT have been found in mammalian cell. They are nucleoplasmic OGT（ ncOGT）,mitochondrial OGT （mOGT） and shorter OGT（sOGT）. We have expressed mOGT in yeast cells with a final goal to study its biological ftinction. A certain number of yeast proteins were clearly revealed in mOGT overexpressed cells, demonstrating the activity of mOGT in yeast cells. Furthermore, it was found that human mOGT protein inhibited the cell growth of yeast. This humanized yeast strain can be used for studying the biological function and the regulation mechanism of human mOGT.
出处
《食品与生物技术学报》
CAS
CSCD
北大核心
2016年第9期987-992,共6页
Journal of Food Science and Biotechnology
基金
教育部科学技术研究重大项目(313027)
中央高校基本科研业务费专项项目(JUSRP311A02)
