Hatano Yuhki, Naoki Koike, Suzuki Asuka, Ushimaru Takashi
Faculty of Biological Science, Shizuoka University, Shizuoka 422-8529, Japan.
Faculty of Biological Science, Shizuoka University, Shizuoka 422-8529, Japan.
Cell Signal. 2016 Oct;28(10):1545-54. doi: 10.1016/j.cellsig.2016.07.005. Epub 2016 Jul 11.
The mitotic inhibitor securin is degraded via the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdc20 after anaphase onset. This triggers activation of the mitotic protease separase and thereby sister chromatid separation. However, only a proportion of securin molecules are degraded at metaphase-anaphase transition and the remaining molecules are still present in anaphase. The roles of securin and separase in late mitosis remain elusive. Here, we show that securin still inhibits separase to repress mitotic exit in anaphase in budding yeast. APC/C-Cdh1-mediated securin degradation at telophase further liberated separase, which promotes Cdc14 release and mitotic exit. Separase executed these events via its proteolytic action and that in the Cdc14 early release (FEAR) network. Cdc14 release further activated APC/C-Cdh1 in the manner of a positive feedback loop. Thus, the positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis. This study shows the importance of the two-step degradation mode of securin and the role of separase in mitotic exit.
有丝分裂抑制剂securin在后期开始后通过泛素连接酶后期促进复合物/细胞周期体（APC/C）-Cdc20降解。这触发了有丝分裂蛋白酶分离酶的激活，从而导致姐妹染色单体分离。然而，只有一部分securin分子在中期-后期转变时被降解，其余分子在后期仍然存在。Securin和分离酶在有丝分裂后期的作用仍然不清楚。在这里，我们表明，在芽殖酵母中，securin在后期仍然抑制分离酶以抑制有丝分裂退出。末期APC/C-Cdh1介导的securin降解进一步释放了分离酶，这促进了Cdc14的释放和有丝分裂退出。分离酶通过其蛋白水解作用以及在Cdc14早期释放（FEAR）网络中的作用来执行这些事件。Cdc14的释放以正反馈回路的方式进一步激活了APC/C-Cdh1。因此，正反馈通过APC/C-Cdh1-分离酶-Cdc14轴促进有丝分裂退出。这项研究表明了securin两步降解模式的重要性以及分离酶在有丝分裂退出中的作用。
