Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic factor arrest
Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic factor arrest
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DOI：
10.1073/pnas.0405300101
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发表时间：
2004-08-24
影响因子：
11.1
通讯作者：
Kishimoto, T
中科院分区：
文献类型：
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作者：
Ohsumi, K;Koyanagi, A;Kishimoto, T
大多数脊椎动物的卵母细胞在第二次减数分裂中期（meta-II）停止，等待受精，从而阻止孤雌激活。这种停滞是由一种称为细胞生长抑制因子（CSF）的细胞质活性引起的，该因子在30年前首次在蛙蛙卵母细胞中发现。CSF阻滞主要通过防止细胞周期蛋白B的破坏而维持细胞周期蛋白B-Cdc 2的活性在升高的水平。尽管CSF阻滞是由Mos-丝裂原活化蛋白激酶途径建立的，并由Ca-钙调蛋白激酶II途径释放，但仍不清楚细胞周期蛋白B的破坏是如何精确调节的。最近，早期有丝分裂抑制剂，ESTA 1，是CSF的一个重要组成部分。这份报告已被期望提供一个最终的解决方案，CSF的问题，因为EST 1抑制后期促进复合物/细胞周期体，泛素连接酶的细胞周期蛋白B破坏，通过螯合Cdc 20，一个激活剂的后期促进复合物/细胞周期体。然而，在有丝分裂周期中，在每一个前中期都破坏了CSF 1，因此，目前还不清楚为什么CSF 1应该是CSF活性所必需的，这只在meta-II中看到。在这里，我们表明，在未受精的成熟非洲爪蟾卵，外源性的EST 1是不存在的元II和有丝分裂中期被破坏。在卵母细胞中表达的EST 1阻碍减数分裂进程。尽管Mos和BMP 1都可以抑制M期的进展，但BMP 1介导的阻滞不需要丝裂原活化蛋白激酶活性，也不被Ca释放。总之，我们的研究结果表明，BMP 1不太可能是CSF的一个组成部分。
Oocytes of most vertebrates arrest at metaphase of the second meiosis (meta-II) to await fertilization, thus preventing parthenogenetic activation. This arrest is caused by a cytoplasmic activity called cytostatic factor (CSF), which was first identified in the frog Rana pipiens oocyte >30 years ago. CSF arrest is executed by maintaining the activity of cyclin B-Cdc2 at elevated levels largely through prevention of cyclin B destruction. Although CSF arrest is established by the Mos-mitogen-activated protein kinase pathway and is released by the Ca-calmodulin kinase II pathway, it remains unclear precisely how cyclin B destruction is regulated. Recently, an early mitotic inhibitor, Emi1, was reported to be a critical component of CSF. This report has been expected to provide a final resolution to the CSF problem because Emi1 inhibits the anaphase-promoting complex/cyclosome, a ubiquitin ligase for cyclin B destruction, through sequestration of Cdc20, an activator for the anaphase-promoting complex/cyclosome. In mitotic cycles, however, Emi1 is destroyed in every pro-metaphase, and accordingly, it is unclear why Emi1 should be required for CSF activity, which is seen only in meta-II. Here, we show that Emi1 is absent in unfertilized mature Xenopus eggs and that exogenous Emi1 is destroyed in meta-II and mitotic metaphase. The expression of Emi1 in oocytes hinders meiotic progression. Although both Emi1 and Mos can inhibit progression through M phase, the Emi1-mediated arrest does not require mitogen-activated protein kinase activity and is not released by Ca. Together, our results indicate that Emi1 is unlikely to be a component of CSF.