Randall Centre for Cell and Molecular Biophysics, King's College London, London, SE1 1UL, UK.
Faculty of Medicine, Institute for Computational Biomedicine, Bioquant, Heidelberg University, 69120, Heidelberg, Germany.
Sci Rep. 2021 May 27;11(1):11122. doi: 10.1038/s41598-021-90384-3.
In eukaryotes the entry into mitosis is initiated by activation of cyclin-dependent kinases (CDKs), which in turn activate a large number of protein kinases to induce all mitotic processes. The general view is that kinases are active in mitosis and phosphatases turn them off in interphase. Kinases activate each other by cross- and self-phosphorylation, while phosphatases remove these phosphate groups to inactivate kinases. Crucial exceptions to this general rule are the interphase kinase Wee1 and the mitotic phosphatase Cdc25. Together they directly control CDK in an opposite way of the general rule of mitotic phosphorylation and interphase dephosphorylation. Here we investigate why this opposite system emerged and got fixed in almost all eukaryotes. Our results show that this reversed action of a kinase-phosphatase pair, Wee1 and Cdc25, on CDK is particularly suited to establish a stable G2 phase and to add checkpoints to the cell cycle. We show that all these regulators appeared together in LECA (Last Eukaryote Common Ancestor) and co-evolved in eukaryotes, suggesting that this twist in kinase-phosphatase regulation was a crucial step happening at the emergence of eukaryotes.
在真核生物中，有丝分裂的进入是由细胞周期蛋白依赖性激酶（CDK）的激活引发的，CDK 又激活了大量的蛋白激酶，以诱导所有有丝分裂过程。一般认为，激酶在有丝分裂中活跃，而磷酸酶在间期使它们失活。激酶通过交叉和自我磷酸化激活彼此，而磷酸酶则去除这些磷酸基团使激酶失活。这种普遍规则的关键例外是间期激酶 Wee1 和有丝分裂磷酸酶 Cdc25。它们共同以与有丝分裂磷酸化和间期去磷酸化的普遍规则相反的方式直接控制 CDK。在这里，我们研究了为什么这个相反的系统会出现在几乎所有的真核生物中，并固定下来。我们的结果表明，这种激酶-磷酸酶对 CDK 的相反作用，Wee1 和 Cdc25，特别适合建立稳定的 G2 期，并为细胞周期添加检查点。我们表明，所有这些调节剂都出现在 LECA（最后真核生物共同祖先）中，并在真核生物中共同进化，这表明这种激酶-磷酸酶调控的扭曲是真核生物出现时的一个关键步骤。
