Cell Division Biology Group, Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Cell Division Biology Group, Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Dev Cell. 2019 Mar 11;48(5):672-684.e5. doi: 10.1016/j.devcel.2019.01.008. Epub 2019 Feb 7.
Successful mitosis requires that cyclin B1:CDK1 kinase activity remains high until chromosomes are correctly aligned on the mitotic spindle. It has therefore been unclear why, in mammalian oocyte meiosis, cyclin B1 destruction begins before chromosome alignment is complete. Here, we resolve this paradox and show that mouse oocytes exploit an imbalance in the ratio of cyclin B1 to CDK1 to control CDK1 activity; early cyclin B1 destruction reflects the loss of an excess of non-CDK1-bound cyclin B1 in late prometaphase, while CDK1-bound cyclin B1 is destroyed only during metaphase. The ordered destruction of the two forms of cyclin B1 is brought about by a previously unidentified motif that is accessible in free cyclin B1 but masked when cyclin B1 is in complex with CDK1. This protects the CDK1-bound fraction from destruction in prometaphase, ensuring a period of prolonged CDK1 activity sufficient to achieve optimal chromosome alignment and prevent aneuploidy.
有丝分裂的成功进行要求细胞周期蛋白 B1:CDK1 激酶活性保持在高水平，直到染色体在有丝分裂纺锤体上正确排列。因此，哺乳动物卵母细胞减数分裂中，为什么在染色体完全对齐之前就开始破坏细胞周期蛋白 B1 一直不清楚。在这里，我们解决了这个矛盾，表明小鼠卵母细胞利用细胞周期蛋白 B1 与 CDK1 的比例失衡来控制 CDK1 活性；早期细胞周期蛋白 B1 的破坏反映了在早中期后期非 CDK1 结合的细胞周期蛋白 B1 的过量损失，而只有在中期才会破坏 CDK1 结合的细胞周期蛋白 B1。两种形式的细胞周期蛋白 B1 的有序破坏是由一个以前未被识别的模体引起的，该模体在游离细胞周期蛋白 B1 中是可访问的，但在与 CDK1 结合时被掩盖。这保护了与 CDK1 结合的部分免受早中期的破坏，确保了一段延长的 CDK1 活性足以实现最佳的染色体对齐并防止非整倍体。
