PKA and MPF-activated polo-like kinase regulate anaphase-promoting complex activity and mitosis progression
PKA and MPF-activated polo-like kinase regulate anaphase-promoting complex activity and mitosis progression
复制标题
DOI：
10.1016/s1097-2765(00)80037-4
复制
发表时间：
1998-02-01
期刊：
影响因子：
16
通讯作者：
Todokoro, K
中科院分区：
文献类型：
--
作者：
Kotani, S;Tugendreich, S;Todokoro, K
泛素介导的蛋白水解是细胞周期调控的关键。后期促进复合物/细胞周期体（APC）是一种泛素连接酶，其靶向细胞周期蛋白B和调节姐妹染色单体分离的因子，用于蛋白酶体的蛋白水解，并因此调节中期-后期转换和退出有丝分裂。在这里，我们报告，Cdc 2-细胞周期蛋白B激活Polo样激酶（Plk）特异性磷酸化至少三个组件的APC和激活APC泛素化细胞周期蛋白B在体外重建系统。相反，蛋白激酶A（PKA）磷酸化APC的两个亚基，但抑制APC活性。PKA对APC的调节作用上级于Plk，Plk活性在细胞分裂中期达到高峰，而PKA活性在中期下降。这些结果表明，Plk和PKA通过控制APC活性来调节有丝分裂进程。
Ubiquitin-mediated proteolysis is the key to cell cycle control. Anaphase-promoting complex/cyclosome (APC) is a ubiquitin ligase that targets cyclin B and factors regulating sister chromatid separation for proteolysis by the proteasome and, consequently, regulates metaphase-anaphase transition and exit from mitosis. Here we report that Cdc2-cyclin B-activated Polo-like kinase (Plk) specifically phosphorylates at least three components of APC and activates APC to ubiquitinate cyclin B in the in vitro-reconstituted system. Conversely, protein kinase A (PKA) phosphorylates two subunits of APC but suppresses APC activity. PKA is superior to Plk in its regulation of APC, and Plk activity peaks whereas PKA activity is falling at metaphase. These results indicate that Plk and PKA regulate mitosis progression by controlling APC activity.