Metaphase arrest by cyclin E-Cdk2 requires the spindle-checkpoint kinase Mps1
Metaphase arrest by cyclin E-Cdk2 requires the spindle-checkpoint kinase Mps1
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DOI：
10.1016/j.cub.2006.08.055
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发表时间：
2006-10-10
期刊：
影响因子：
9.2
通讯作者：
Maller, James L.
中科院分区：
文献类型：
--
作者：
Grimison, Bryn;Liu, Junjun;Maller, James L.
细胞抑制因子 (CSF) 通过抑制后期促进复合物/细胞周期体 (APC/C) 激活的多种途径，将脊椎动物卵阻滞在减数分裂 II 中期 [1-3]。在非洲爪蟾中，Mos-MEK1-MAPK-p90(Rsk) 级联利用纺锤体组装检查点组件来实现中期停滞。另一条途径涉及细胞周期蛋白 E-Cdk2，鸡蛋提取物中持续的细胞周期蛋白 E-Cdk2 活性会在缺乏 Mos 的情况下导致中期停滞；后一项发现表明，有一条独立的途径有助于脑脊液停滞 [4, 5]。在这里，我们证明，细胞周期蛋白 E-Cdk2 的中期停滞需要纺锤体检查点激酶单极纺锤体 1 (Mps1)，它是细胞周期蛋白 E-Cdk2 的靶标，也与中心体复制有关 [6, 7]。 xMps1 在卵母细胞成熟过程中合成并激活，并在脑脊液释放时失活。在鸡蛋提取物中，钙释放的脑脊液被组成型活性细胞周期蛋白 E-Cdk2 抑制，并被野生型 xMps1 延迟。反义寡核苷酸消除细胞周期蛋白 E 可阻止 xMps1 的积累，表明细胞周期蛋白 E-Cdk2 控制 Mps1 水平。在减数分裂II期间，即使在Mos-MAPK途径不存在的情况下，活化的细胞周期蛋白E-Cdk2也能显着抑制APC/C，但这种抑制不足以抑制减数分裂I和II之间的S期。这些结果独特地将 xMps1 置于细胞周期蛋白 E-Cdk2 下游，介导 APC/C 抑制和中期停滞途径。
Cytostatic factor (CSF) arrests vertebrate eggs in metaphase of meiosis II through several pathways that inhibit activation of the anaphase-promoting complex/cyclosome (APC/C) [1-3]. In Xenopus, the Mos-MEK1-MAPK-p90(Rsk) cascade utilizes spindle-assembly-checkpoint components to effect metaphase arrest. Another pathway involves cyclin E-Cdk2, and sustained cyclin E-Cdk2 activity in egg extracts causes metaphase arrest in the absence of Mos; this latter finding suggests that an independent pathway contributes to CSF arrest [4, 5]. Here, we demonstrate that metaphase arrest with cyclin E-Cdk2, but not with Mos, requires the spindle-checkpoint kinase monopolar spindles 1 (Mps1), a cyclin E-Cdk2 target that is also implicated in centrosome duplication [6, 7]. xMps1 is synthesized and activated during oocyte maturation and inactivated upon CSF release. In egg extracts, CSF release by calcium was inhibited by constitutively active cyclin E-Cdk2 and delayed by wild-type xMps1. Ablation of cyclin E by antisense oligonucleotides blocked accumulation of xMps1, suggesting that cyclin E-Cdk2 controls Mps1 levels. During meiosis II, activated cyclin E-Cdk2 significantly inhibited the APC/C even in the absence of the Mos-MAPK pathway, but this inhibition was not sufficient to suppress S phase between melosis I and II. These results uniquely place xMps1 downstream of cyclin E-Cdk2 in mediating a pathway of APC/C inhibition and metaphase arrest.