Aurora2 protein regulated by the anaphase-promoting complex-ubiquitin-proteasome pathway.

人类Aurora 2最初通过其与酵母IPL 1和果蝇Aurora的密切同源性而被鉴定，酵母IPL 1和果蝇Aurora是染色体分离的关键调节因子和在许多肿瘤细胞系中过表达的细胞周期调节的丝氨酸/苏氨酸蛋白激酶。我们分析了100例结直肠癌组织中Aurora 2基因的表达。Aurora 2基因在原发性大肠癌中的过表达率为62%。此外，我们证明了Aurora 2蛋白在哺乳动物细胞中G2/M期释放后迅速降解（半衰期约为2小时）。用蛋白酶体抑制剂处理细胞可以阻断Aurora 2的降解。Aurora 2在体内和体外使用后期促进复合物（APC）被聚泛素化。这些结果表明Aurora 2蛋白通过APC-泛素-蛋白酶体通路进行转化，我们希望APC-泛素-蛋白酶体通路的调控可能有助于肿瘤休眠治疗。

Human Aurora2 was originally identified by its close homology to yeast IPL1 and fly aurora, which are key regulators of chromosome segregation and a cell cycle regulated serine/threonine protein kinase which is overexpressed in many tumor cell lines. We analyzed 100 colorectal cancer specimens for the expresssion of Aurora2 gene. The overexpression of Aurora2 gene was 62 % in primary colorectal cancers. Furthermore, we demonstrated that the Aurora2 protein is degraded rapidly after G2/M phase release in mammalian cells, (a half-life of approximately 2 h). The treatment of the cells with proteasome inhibitors blocks Aurora2 degradation. Aurora2 is polyubiquitinated in vivo and in vitro using anaphase-promoting complex (APC). These results demonstrate that Aurora2 protein js turned over through the APC-ubiquitin-proteasome pathway.We hope that the regulation of APC-ubiquitin-proteasome pathway may be useful for tumor dormancy therapy.