Research Group Modeling of Biological Systems, German Cancer Research Center and BioQuant Center, Im Neuenheimer Feld 280, Heidelberg, Germany.
Trends Cell Biol. 2010 Nov;20(11):634-41. doi: 10.1016/j.tcb.2010.08.012. Epub 2010 Sep 23.
Computational and experimental studies have yielded quantitative insights into the role for multisite phosphorylation, and other protein modifications, in cell function. This work has emphasized the creation of thresholds and switches for cellular decisions. To date, the dynamics of phosphorylation events have been disregarded yet could be equally relevant for cell function. Here, we discuss theoretical predictions about the kinetic functions of multisite phosphorylation in regulatory networks and how these predictions relate to experimental findings. Using DNA replication as an example, we demonstrate that multisite phosphorylations can support coherent origin firing and robustness against rereplication. We suggest that multisite protein modifications provide a molecular mechanism to robustly time cellular events in the cell cycle, the circadian clock and signal transduction.
计算和实验研究为多部位磷酸化以及其他蛋白质修饰在细胞功能中的作用提供了定量的见解。这项工作强调了为细胞决策创建阈值和开关。迄今为止，磷酸化事件的动力学尚未被忽视，但对细胞功能可能同样重要。在这里，我们讨论了关于调节网络中多部位磷酸化的动力学功能的理论预测，以及这些预测如何与实验结果相关。我们以 DNA 复制为例，证明了多部位磷酸化可以支持同源起始点火的一致性和对重复复制的稳健性。我们认为，多部位蛋白质修饰为在细胞周期、生物钟和信号转导中稳健地定时细胞事件提供了一种分子机制。
