Securin and not CDK1/cyclin B1 regulates sister chromatid disjunction during meiosis II in mouse eggs
Securin and not CDK1/cyclin B1 regulates sister chromatid disjunction during meiosis II in mouse eggs
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DOI：
10.1016/j.ydbio.2008.06.036
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发表时间：
2008-09-15
影响因子：
2.7
通讯作者：
Jones, Keith T.
中科院分区：
文献类型：
--
作者：
Nabti, Ibtissem;Reis, Alexandra;Jones, Keith T.
哺乳动物的卵子在受精前一段不确定的时间停留在第二次减数分裂中期（metII）。在此期间（可持续几个小时），姐妹染色单体的持续附着被认为是通过抑制蛋白酶分离酶来实现的。已知分离酶通过结合 securin 或成熟（M 相）促进因子（CDK1/细胞周期蛋白 B1 的异二聚体）而受到抑制。然而，尚未评估 securin 和 CDK/cyclin B1 在 metII 停滞期间对姐妹染色单体附着的相对贡献。尽管在某些情况下，CDK1/cyclinB1 活性或 securin 可以防止姐妹染色单体分离（主要是通过不可降解的细胞周期蛋白 B1 或 securin 的过度表达），但我们在此发现分离酶活性主要由 securin 而不是 CDK1/cyclin B1 调节。因此，CDK1 抑制剂 roscovitine 和我们设计的用于阻断 DK1/cyclin B1 与分离酶相互作用的抗体都未能诱导姐妹分离。相比之下，securin 吗啉敲低会特异性诱导姐妹附着的丧失，而这种损失可以通过 securin cRNA 救援来恢复。在 metill 停滞期间，分离酶似乎主要受 securin 结合调节，而不是 CDK1/cyclin B1。 (C) 2008 Elsevier Inc. 保留所有权利。
Mammalian eggs remain arrested at metaphase of the second meiotic division (metII) for an indeterminate time before fertilization. During this period, which can last several hours, the continued attachment of sister chromatids is thought to be achieved by inhibition of the protease separase. Separase is known to be inhibited by binding either securin or Maturation (M-Phase)-Promoting Factor, a heterodimer of CDK1/cyclin B1. However, the relative contribution of securin and CDK/cyclin B1 to sister chromatid attachment during metII arrest has not been assessed. Although there are conditions in which either CDK1/cyclinB1 activity or securin can prevent sister chromatid disjunction, principally by overexpression of non-degradable cyclin B1 or securin, we find here that separase activity is primarily regulated by securin and not CDK1/cyclin B1. Thus the CDK1 inhibitor roscovitine and an antibody we designed to block the interaction of DK1/cyclin B1 with separase, both failed to induce sister disjunction. In contrast, securin morpholino knockdown specifically induced loss of sister attachment, that could be restored by securin cRNA rescue. During metill arrest separase appears primarily regulated by securin binding, not CDK1/cyclin B1. (C) 2008 Elsevier Inc. All rights reserved.