【作者】 李军锋；

【导师】 韩骅；

【作者基本信息】 第四军医大学 ， 发育生物学， 2006， 博士

【摘要】 泛素-蛋白酶体途径被认为是在哺乳动物细胞中选择性的降解短寿命蛋白的主要系统。受调节蛋白主要与细胞周期进程、应激反应、抗原呈递、信号传导、转录调控、DNA损伤修复、凋亡、细胞器官的生物发生有关。泛素化是一系列酶级联传递泛素的结果。具体过程为，泛素激活酶E1催化泛素与底物蛋白结合，即以ATP依赖的方式通过硫醇酯键将泛素的C-端硫醇基与自身的半胱氨酸结合，然后将活化的泛素传递给泛素结合酶E2；泛素连接酶E3将结合着泛素的泛素结合酶和底物蛋白连接，从而促进泛素的羧基末端的甘氨酸与底物蛋白内部的赖氨酸ε的氨基之间形成异肽键，泛素与蛋白结合；部分底物蛋白尚需要多聚泛素化聚集因子E4参与多聚泛素链的形成。之后，泛素多聚链的蛋白分子被26S蛋白酶复合体识别和降解，泛素-C-末端水解酶或者异肽酶酶解释放泛素分子。 UbcH8是人的泛素结合酶基因UBE2L6编码的蛋白，属于主要包含Ubc结构域的第一类泛素结合酶家族(Class Ⅰ E2s)成员。第一类泛素结合酶家族分子不能将泛素分子直接传递给底物蛋白，提示这类E2需要借助泛素连接酶E3进行底物蛋白的识别。研究表明：UbcH8可以与RING finger或者BR motif-containing domain (in between RING fingers)以及HECT[6]等结构域的蛋白发生相互更多还原

【Abstract】 In mammalian cells, the ubiquitin-proteasome pathway is the principal system that mediates selectively the degradation of short-lived proteins related to such cellular activities as cell cycle progression, the response to stress, antigen processing, signal transduction, transcriptional regulation, DNA repair, apoptosis, and organelle biogenesis. Ubiquitylation occurs as a result of the sequential action of four classes of enzymes, E1 or ubiquitin activating enzyme, E2 or ubiquitin conjugating enzyme, E3 or ubiquitin protein ligase and E4 or ubiquitin chain assembly factor. E1, the first enzyme in the ubiquitylation pathway, forms a thiol-ester bond between its active site cysteine and the carboxyl-terminal glycine of ubiquitin. The activated ubiquitin on E1 is subsequently transferred to the active site cysteine of an E2 by transesterification. E3 binds ubiquitin-charged E2 and substrate and facilitates formation of an isopeptide linkage between the carboxyl-terminal glycine of ubiquitin and the ε amino group of an internal lysine residue on the substrate, or an ubiquitin already attached to the protein. Ubiquitin chain assembly factor or E4 is更多还原