Hec1-dependent cyclin B2 stabilization regulates the G2-M transition and early prometaphase in mouse oocytes.
Hec1-dependent cyclin B2 stabilization regulates the G2-M transition and early prometaphase in mouse oocytes.
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DOI：
10.1016/j.devcel.2013.02.008
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发表时间：
2013-04-15
影响因子：
11.8
通讯作者：
Homer, Hayden
中科院分区：
文献类型：
--
作者：
Gui, Liming;Homer, Hayden
高度保守的Ndc80动粒复合体的Ndc80/Hec1亚基在发挥着基于动粒的关键作用时，其功能通常被限制在M期。在这里，我们发现在小鼠卵母细胞中，由于细胞周期蛋白依赖性激酶1(CDK1)的激活受损，Hec1的缺失严重影响了G2-M的转变。出乎意料的是，进入M期的障碍是由于CDK1激活亚基Cyclin B2的不稳定，而Cyclin B1无法覆盖该亚基。Hec1保护细胞周期蛋白B2不被CDH1激活的后期促进复合体(APCCDh1)破坏，并且在无着丝体纺锤体组装的初始阶段，Hec1对细胞周期蛋白B2在早期M期的稳定仍然重要。然而，到M期晚期，Hec1和Cyclin B2解偶联，虽然Hec1保持稳定，但APCCdc20触发了Cyclin B2的破坏。这些数据证实了Hec1功能的另一个维度，以M期进入和早期中期进展为中心，并挑战了周期蛋白B2在哺乳动物中完全不可缺少的观点。在小鼠卵母细胞中，►通过细胞周期蛋白B2稳定细胞周期蛋白B2，对CDK1的激活起重要作用。►细胞周期蛋白B2依赖于细胞周期蛋白B2，稳定细胞周期蛋白B2是早期纺锤体组装所必需的。►HEC1‘基于动粒的作用促进晚期纺锤体组装。►HEC1是NDC80动粒复合体的一个亚单位，最为人所知的是在M期将动粒连接到微管。Gui和Hmer发现，在小鼠卵母细胞中，Hec1在稳定Cyclin B2方面发挥着不依赖动粒的作用，后者促进了G2-M转变和减数分裂I期间早期无着丝粒纺锤体的组装。
The functions of the Ndc80/Hec1 subunit of the highly conserved Ndc80 kinetochore complex are normally restricted to M phase when it exerts a pivotal kinetochore-based role. Here, we find that in mouse oocytes, depletion of Hec1 severely compromises the G2-M transition because of impaired activation of cyclin-dependent kinase 1 (Cdk1). Unexpectedly, impaired M phase entry is due to instability of the Cdk1-activating subunit, cyclin B2, which cannot be covered by cyclin B1. Hec1 protects cyclin B2 from destruction by the Cdh1-activated anaphase-promoting complex (APCCdh1) and remains important for cyclin B2 stabilization during early M phase, required for the initial stages of acentrosomal spindle assembly. By late M phase, however, Hec1 and cyclin B2 become uncoupled, and although Hec1 remains stable, APCCdc20 triggers cyclin B2 destruction. These data identify another dimension to Hec1 function centered on M phase entry and early prometaphase progression and challenge the view that cyclin B2 is completely dispensable in mammals. ► Hec1 stabilizes cyclin B2 against APCCdh1-mediated destruction in mouse oocytes ► Hec1, through cyclin B2, is important for Cdk1 activation at the G2-M transition ► Hec1-dependent cyclin B2 stabilization is required for early-stage spindle assembly ► Hec1’s kinetochore-based role promotes late-stage spindle assembly Hec1 is a subunit of the Ndc80 kinetochore complex best known for linking kinetochores to microtubules during M phase. Gui and Homer find that in mouse oocytes, Hec1 plays a kinetochore-independent role in stabilizing cyclin B2, which promotes the G2-M transition and early-stage acentrosomal spindle assembly during meiosis I.
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DOI：
10.1016/j.cub.2008.08.012
发表时间：
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期刊：
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