Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Dev Cell. 2012 Apr 17;22(4):763-74. doi: 10.1016/j.devcel.2012.01.019. Epub 2012 Apr 5.
Cells commit to mitosis by abruptly activating the mitotic cyclin-Cdk complexes. During Drosophila gastrulation, mitosis is associated with the transcriptional activation of cdc25(string), a phosphatase that activates Cdk1. Here, we demonstrate that the switch-like entry into mitosis observed in the Drosophila embryo during the 14(th) mitotic cycle is timed by the dynamics of Cdc25(string) accumulation. The switch operates as a short-term integrator, a property that can improve the reliable control of timing of mitosis. The switch is independent of the positive feedback between Cdk1 and Cdc25(string) and of the double negative feedback between Cdk1 and Wee1. We propose that the properties of the mitotic switch are established by the out-of-equilibrium properties of the covalent modification cycle controlling Cdk1 activity. Such covalent modification cycles, triggered by transcriptional expression of the activating enzymes, might be a widespread strategy to obtain reliable and switch-like control of cell decisions.
细胞通过突然激活有丝分裂周期蛋白-Cdk 复合物来决定进行有丝分裂。在果蝇胚胎发生过程中，有丝分裂伴随着细胞分裂周期蛋白 25（string）的转录激活，这是一种激活 Cdk1 的磷酸酶。在这里，我们证明在果蝇胚胎的第 14 次有丝分裂周期中观察到的类似于开关的有丝分裂进入是由 Cdc25（string）积累的动态决定的。该开关作为短期积分器运作，这一特性可以提高有丝分裂时间控制的可靠性。该开关独立于 Cdk1 和 Cdc25（string）之间的正反馈以及 Cdk1 和 Wee1 之间的双负反馈。我们提出，有丝分裂开关的特性是由控制 Cdk1 活性的共价修饰循环的非平衡特性决定的。这种由激活酶的转录表达触发的共价修饰循环可能是获得可靠的、类似于开关的细胞决策控制的广泛策略。
