Echard Arnaud, O'Farrell Patrick H
Department of Biochemistry and Biophysics, University of California, San Francisco, Genentech Hall, 600 16th Street, San Francisco, CA 94143, USA.
Curr Biol. 2003 Mar 4;13(5):373-83. doi: 10.1016/s0960-9822(03)00127-1.
Cytokinesis occurs just as chromosomes complete segregation and reform nuclei. It has been proposed that cyclin/Cdk kinase inhibits cytokinesis until exit from mitosis; however, the timer of cytokinesis has not been experimentally defined. Whereas expression of a stable version of Drosophila cyclin B blocks cytokinesis along with numerous events of mitotic exit, stable cyclin B3 allows cytokinesis even though it blocks late events of mitotic exit. We examined the interface between mitotic cyclin destruction and the timing of cytokinesis.
In embryonic mitosis 14, the cytokinesis furrow appeared 60 s after the metaphase/anaphase transition and closed 90 s later during telophase. In cyclin B or cyclin B3 mutant cells, the cytokinesis furrow appeared at an earlier stage of mitosis. Expression of stable cyclin B3 delayed and prolonged furrow invagination; nonetheless, cytokinesis completed during the extended mitosis. Reduced function of Pebble, a Rho GEF required for cytokinesis, also delayed and slowed furrow invagination, but incomplete furrows were aborted at the time of mitotic exit. In functional and genetic tests, cyclin B and cyclin B3 inhibited Pebble contributions to cytokinesis.
Temporal coordination of mitotic events involves inhibition of cytokinesis by cyclin B and cyclin B3 and punctual relief of the inhibition by destruction of these cyclins. Both cyclins inhibit Pebble-dependent activation of cytokinesis, whereas cyclin B can inhibit cytokinesis by additional modes. Stable cyclin B3 also blocks the later return to interphase that otherwise appears to impose a deadline for the completion of cytokinesis.
胞质分裂发生在染色体完成分离并重新形成细胞核之时。有人提出细胞周期蛋白/细胞周期蛋白依赖性激酶（Cdk）抑制胞质分裂，直至有丝分裂退出；然而，胞质分裂的时间调控尚未通过实验确定。虽然果蝇细胞周期蛋白B的稳定版本的表达会阻断胞质分裂以及许多有丝分裂退出事件，但稳定的细胞周期蛋白B3尽管会阻断有丝分裂退出的后期事件，却允许胞质分裂发生。我们研究了有丝分裂细胞周期蛋白降解与胞质分裂时间调控之间的关系。
在胚胎有丝分裂14期，胞质分裂沟在中期/后期转换后60秒出现，并在末期90秒后闭合。在细胞周期蛋白B或细胞周期蛋白B3突变细胞中，胞质分裂沟在有丝分裂的更早阶段出现。稳定的细胞周期蛋白B3的表达延迟并延长了沟的内陷；尽管如此，胞质分裂在延长的有丝分裂过程中完成。Pebble是胞质分裂所需的一种Rho鸟嘌呤核苷酸交换因子（GEF），其功能降低也会延迟并减缓沟的内陷，但不完全的沟在有丝分裂退出时会中止。在功能和遗传学测试中，细胞周期蛋白B和细胞周期蛋白B3抑制了Pebble对胞质分裂的作用。
有丝分裂事件的时间协调涉及细胞周期蛋白B和细胞周期蛋白B3对胞质分裂的抑制以及这些细胞周期蛋白降解后对抑制的适时解除。两种细胞周期蛋白都抑制Pebble依赖性的胞质分裂激活，而细胞周期蛋白B还可通过其他方式抑制胞质分裂。稳定的细胞周期蛋白B3还会阻断后期向间期的恢复，否则这似乎会为胞质分裂的完成设定一个期限。
