Ciliberto Andrea, Petrus Matthew J, Tyson John J, Sible Jill C
Biology Department, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0406, USA.
Biophys Chem. 2003 Jul 1;104(3):573-89. doi: 10.1016/s0301-4622(03)00060-7.
Early cell cycles of Xenopus laevis embryos are characterized by rapid oscillations in the activity of two cyclin-dependent kinases. Cdk1 activity peaks at mitosis, driven by periodic degradation of cyclins A and B. In contrast, Cdk2 activity oscillates twice per cell cycle, despite a constant level of its partner, cyclin E. Cyclin E degrades at a fixed time after fertilization, normally corresponding to the midblastula transition. Based on published data and new experiments, we constructed a mathematical model in which: (1) oscillations in Cdk2 activity depend upon changes in phosphorylation, (2) Cdk2 participates in a negative feedback loop with the inhibitory kinase Wee1; (3) cyclin E is cooperatively removed from the oscillatory system; and (4) removed cyclin E is degraded by a pathway activated by cyclin E/Cdk2 itself. The model's predictions about embryos injected with Xic1, a stoichiometric inhibitor of cyclin E/Cdk2, were experimentally validated.
非洲爪蟾胚胎的早期细胞周期的特征是两种细胞周期蛋白依赖性激酶的活性快速振荡。Cdk1活性在有丝分裂时达到峰值，由细胞周期蛋白A和B的周期性降解驱动。相比之下，Cdk2活性在每个细胞周期振荡两次，尽管其伴侣细胞周期蛋白E的水平恒定。细胞周期蛋白E在受精后的固定时间降解，通常对应于囊胚中期转换。基于已发表的数据和新的实验，我们构建了一个数学模型，其中：（1）Cdk2活性的振荡取决于磷酸化的变化；（2）Cdk2与抑制性激酶Wee1参与一个负反馈回路；（3）细胞周期蛋白E从振荡系统中协同去除；（4）去除的细胞周期蛋白E通过由细胞周期蛋白E/Cdk2自身激活的途径降解。该模型关于注射了Xic1（细胞周期蛋白E/Cdk2的化学计量抑制剂）的胚胎的预测得到了实验验证。
