The Gurdon Institute, Cambridge, England, UK.
Department of Zoology, University of Cambridge, Cambridge, England, UK.
J Cell Biol. 2018 Jan 2;217(1):179-193. doi: 10.1083/jcb.201612147. Epub 2017 Oct 26.
There is remarkable redundancy between the Cyclin-Cdk complexes that comprise the cell cycle machinery. None of the mammalian A-, D-, or E-type cyclins are required in development until implantation, and only Cdk1 is essential for early cell divisions. Cyclin B1 is essential for development, but whether it is required for cell division is contentious. Here, we used a novel imaging approach to analyze Cyclin B1-null embryos from fertilization onward. We show that Cyclin B1 embryos arrest in G2 phase after just two divisions. This is the earliest arrest of any Cyclin known and places Cyclin B1 with cdk1 as the essential regulators of the cell cycle. We reintroduced mutant proteins into this genetically null background to determine why Cyclin B1 is constantly exported from the nucleus. We found that Cyclin B1 must be exported from the nucleus for the cell to prevent premature entry to mitosis, and retaining Cyclin B1-Cdk1 at the plasma membrane precludes entry to mitosis.
细胞周期机制所包含的细胞周期蛋白-Cdk 复合物之间存在显著的冗余。在植入之前，哺乳动物的 A、D 或 E 型细胞周期蛋白都不需要在发育过程中，只有 Cdk1 对早期细胞分裂是必不可少的。细胞周期蛋白 B1 对发育是必不可少的，但它是否对细胞分裂是必需的存在争议。在这里，我们使用一种新的成像方法来分析从受精开始的细胞周期蛋白 B1 缺失胚胎。我们发现细胞周期蛋白 B1 胚胎在仅仅两次分裂后就停留在 G2 期。这是已知的最早的细胞周期蛋白阻滞，将细胞周期蛋白 B1 与 cdk1 一起定位为细胞周期的必需调节剂。我们将突变蛋白重新引入这个遗传缺失背景，以确定为什么细胞周期蛋白 B1 会不断从核内输出。我们发现，为了防止过早进入有丝分裂，细胞必须将细胞周期蛋白 B1 从核内输出，并且将细胞周期蛋白 B1-Cdk1 保留在质膜上可以防止进入有丝分裂。
