A mutual inhibition between APC/C and its substrate Mes1 required for meiotic progression in fission yeast
A mutual inhibition between APC/C and its substrate Mes1 required for meiotic progression in fission yeast
复制标题
DOI：
10.1016/j.devcel.2007.12.010
复制
发表时间：
2008-03-01
影响因子：
11.8
通讯作者：
Yamano, Hiroyuki
中科院分区：
文献类型：
--
作者：
Kimata, Yuu;Trickey, Michelle;Yamano, Hiroyuki
后期促进复合物/环体（APC/C）是一种细胞周期调节必需的E3泛素连接酶，然而，很少有人知道它的减数分裂调控。在这里，我们表明，裂殖酵母Mes 1是APC/C的底物以及抑制剂，允许APC/C在减数分裂中的自动调节。这两种特质都需要一个功能性的破坏盒（D盒）和KEN盒。我们发现，Mes 1直接结合APC/C激活剂的Fizzy家族的WD 40结构域。有趣的是，nonubiquitylatable Mes 1的表达阻断了具有高水平APC/C底物的中期I细胞，这表明Mes 1的泛素化是通过减轻Mes 1抑制功能来部分降解减数分裂I中的细胞周期蛋白B所必需的。同时，APC/C-Fizzy/Cdc 20-Mes 1三元复合物通过抑制Mes 1泛素化而稳定。这些结果表明，APC/C活性的微调，也是一种抑制剂的底物，是通过减数分裂的精确协调和过渡所必需的。
The anaphase-promoting complex/cyclosome (APC/C) is a cell-cycle-regulated essential E3 ubiquitin ligase; however, very little is known about its meiotic regulation. Here we show that fission yeast Mes1 is a substrate of the APC/C as well as an inhibitor, allowing autoregulation of the APC/C in meiosis. Both traits require a functional destruction box (D box) and KEN box. We show that Mes1 directly binds the WD40 domain of the Fizzy family of APC/C activators. Intriguingly, expression of nonubiquitylatable Mes1 blocks cells in metaphase I with high levels of APC/C substrates, suggesting that ubiquitylation of Mes1 is required for partial degradation of cyclin B in meiosis I by alleviating Mes1 inhibitory function. Consistently, a ternary complex, APC/C-Fizzy/Cdc20-Mes1, is stabilized by inhibiting Mes1 ubiquitylation. These results demonstrate that the fine-tuning of the APC/C activity, by a substrate that is also an inhibitor, is required for the precise coordination and transition through meiosis.