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

Aurora2 蛋白受后期促进复合物-泛素-蛋白酶体途径调节。

• 批准号: 12671214
• 负责人: ISHIDA Makoto
• 金额: $ 1.73万
• 依托单位: 福井医科大学
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671214/
• 关键词: Aurora2; gl-rine; threonine protein; ubiquitination; APC-ubiquitin-proteasome pathway; スレオニンキナーゼ; Aurora2; Colorectal Cancer

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.

人类 Aurora2 最初是通过其与酵母 IPL1 和果蝇 aurora 的密切同源性而被识别的，它们是染色体分离的关键调节因子和细胞周期调节的丝氨酸/苏氨酸蛋白激酶，在许多肿瘤细胞系中过度表达。我们分析了 100 份结直肠癌标本中 Aurora2 基因的表达情况。 Aurora2基因在原发性结直肠癌中的过度表达率为62%。此外，我们证明 Aurora2 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阻止 Aurora2 降解。 Aurora2 使用后期促进复合物 (APC) 在体内和体外进行多泛素化。这些结果表明Aurora2蛋白是通过APC-泛素-蛋白酶体途径进行翻转的。我们希望APC-泛素-蛋白酶体途径的调控可能有助于肿瘤休眠治疗。