Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) in yeast that controls spore differentiation. It is activated by a MAPK binding protein, Ssp2, upon completion of the meiotic divisions. The activation of Smk1 by Ssp2 is positively regulated by a meiosis-specific coactivator of the anaphase promoting complex (APC/C) E3 ubiquitin ligase, Ama1. Here, we identify Isc10 as an inhibitor that links APC/CAma1 to Smk1 activation. Isc10 and Smk1 form an inhibited complex during meiosis I (MI). Ssp2 is produced later in the program, and it forms a ternary complex with Isc10 and Smk1 during MII that is poised for activation. Upon completion of MII, Isc10 is ubiquitylated and degraded in an AMA1-dependent manner, thereby triggering the activation of Smk1 by Ssp2. Mutations that caused Ssp2 to be produced before MII, or isc10Δ mutations, modestly reduced the efficiency of spore differentiation whereas spores were nearly absent in the double mutant. These findings define a pathway that couples spore differentiation to the G0-like phase of the cell cycle.

中文翻译：

---

Isc10，一种将后期促进复合物与减数分裂特异性丝裂原活化蛋白激酶连接起来的抑制剂。

Smk1 是酵母中控制孢子分化的减数分裂特异性丝裂原活化蛋白激酶 (MAPK)。在减数分裂完成后，它被 MAPK 结合蛋白 Ssp2 激活。Ssp2 对 Smk1 的激活受到后期促进复合物 (APC/C) E3 泛素连接酶 Ama1 的减数分裂特异性共激活剂的正向调节。在这里，我们将 Isc10 确定为将 APC/CAma1 与 Smk1 激活联系起来的抑制剂。Isc10 和 Smk1 在减数分裂 I (MI) 期间形成抑制复合物。Ssp2 在程序的后期生成，它在准备激活的 MII 期间与 Isc10 和 Smk1 形成三元复合物。MII 完成后，Isc10 泛素化并以 AMA1 依赖性方式降解，从而触发 Ssp2 对 Smk1 的激活。导致 Ssp2 在 MII 或 isc10Δ 突变之前产生的突变，适度降低孢子分化的效率，而双突变体中几乎不存在孢子。这些发现定义了一种将孢子分化与细胞周期的 G0 样期相结合的途径。