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一种使用可逆结合抑制剂控制细胞周期动力学的理论。

A theory for controlling cell cycle dynamics using a reversibly binding inhibitor.

作者信息

Gardner T S, Dolnik M, Collins J J

机构信息

Center for BioDynamics and Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA.

出版信息

Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14190-5. doi: 10.1073/pnas.95.24.14190.

Abstract

We demonstrate, by using mathematical modeling of cell division cycle (CDC) dynamics, a potential mechanism for precisely controlling the frequency of cell division and regulating the size of a dividing cell. Control of the cell cycle is achieved by artificially expressing a protein that reversibly binds and inactivates any one of the CDC proteins. In the simplest case, such as the checkpoint-free situation encountered in early amphibian embryos, the frequency of CDC oscillations can be increased or decreased by regulating the rate of synthesis, the binding rate, or the equilibrium constant of the binding protein. In a more complex model of cell division, where size-control checkpoints are included, we show that the same reversible binding reaction can alter the mean cell mass in a continuously dividing cell. Because this control scheme is general and requires only the expression of a single protein, it provides a practical means for tuning the characteristics of the cell cycle in vivo.

摘要

我们通过对细胞分裂周期(CDC)动力学进行数学建模,展示了一种精确控制细胞分裂频率和调节分裂细胞大小的潜在机制。通过人工表达一种能可逆结合并使任何一种CDC蛋白失活的蛋白质来实现对细胞周期的控制。在最简单的情况下,比如早期两栖动物胚胎中遇到的无检查点情况,通过调节结合蛋白的合成速率、结合速率或平衡常数,可以增加或降低CDC振荡的频率。在一个更复杂的包含大小控制检查点的细胞分裂模型中,我们表明相同的可逆结合反应可以改变连续分裂细胞的平均细胞质量。由于这种控制方案具有通用性,且只需要表达一种蛋白质,它为在体内调节细胞周期特性提供了一种实用手段。

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