At mitotic exit the cell cycle engine is reset to allow crucial processes, such as cytokinesis and replication origin licensing, to take place before a new cell cycle begins. In budding yeast, the cell cycle clock is reset by a Hippo-like kinase cascade called the mitotic exit network (MEN), whose activation is triggered at spindle pole bodies (SPBs) by the Tem1 GTPase. Yet, MEN activity must be extinguished once MEN-dependent processes have been accomplished. One factor contributing to switching off the MEN is the Amn1 protein, which binds Tem1 and inhibits it through an unknown mechanism. Here, we show that Amn1 downregulates Tem1 through a dual mode of action. On one side, it evicts Tem1 from SPBs and escorts it into the nucleus. On the other, it promotes Tem1 degradation as part of a Skp, Cullin and F-box-containing (SCF) ubiquitin ligase. Tem1 inhibition by Amn1 takes place after cytokinesis in the bud-derived daughter cell, consistent with its asymmetric appearance in the daughter cell versus the mother cell. This dual mechanism of Tem1 inhibition by Amn1 may contribute to the rapid extinguishing of MEN activity once it has fulfilled its functions.

中文翻译：

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胞质分裂后 Amn1 对 Tem1 GTPase 的下调涉及核输入和 SCF 介导的降解。

在有丝分裂退出时，细胞周期引擎被重置以允许关键过程，例如胞质分裂和复制起源许可，在新的细胞周期开始之前发生。在出芽酵母中，细胞周期时钟由称为有丝分裂出口网络 (MEN) 的类似河马的激酶级联重新设置，其激活由 Tem1 GTP 酶在纺锤体极体 (SPB) 处触发。然而，一旦完成了依赖于 MEN 的过程，就必须终止 MEN 活动。导致关闭 MEN 的一个因素是 Amn1 蛋白，它与 Tem1 结合并通过未知机制抑制它。在这里，我们表明 Amn1 通过双重作用模式下调 Tem1。一方面，它将 Tem1 从 SPB 中驱逐出来，并护送它进入细胞核。另一方面，它作为 Skp、Cullin 和含 F-box (SCF) 泛素连接酶的一部分促进 Tem1 降解。Amn1 对 Tem1 的抑制发生在芽衍生的子细胞胞质分裂后，与其在子细胞与母细胞中的不对称外观一致。这种 Amn1 抑制 Tem1 的双重机制可能有助于 MEN 活动一旦完成其功能就会迅速消失。