The logic of the Membrane, Magnesium, Mitosis (MMM) model for the regulation of animal cell proliferation
The logic of the Membrane, Magnesium, Mitosis (MMM) model for the regulation of animal cell proliferation
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DOI：
10.1016/j.abb.2006.03.026
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发表时间：
2007-02-01
影响因子：
3.9
通讯作者：
Rubin, Harry
中科院分区：
文献类型：
--
作者：
Rubin, Harry
在静止的、无血清的脊椎动物细胞中加入动物血清或特定的蛋白质生长因子，可以在几分钟内激活各种生化反应，随后在5-10小时内启动DNA合成，然后有丝分裂。DNA合成增加的典型早期和持续激活步骤是蛋白质合成起始率的提高，蛋白质合成必须在整个G1期持续保持才能进入S期。对生长因子的生化反应的集合被称为协调反应，以表明许多相关和无关的过程被协调以复制细胞。然而，重要的是要认识到，对于一轮或多轮复制，协调反应可以由各种非特异性和准特异性膜效应器诱导。在生长控制中考虑这一事件框架的逻辑意味着，单一的多目标第二信使在协调整个反应的事件方面发挥着中心作用。同样的推理表明，在包括蛋白激酶途径的反应中，游离镁离子是统一的调节元件，并且随着生长因子与细胞膜上它们的受体的结合或膜上较不特异的扰动，镁离子的细胞质活性增加。这一结论在实验上得到了支持，并体现在细胞增殖控制的MMM模型中。(C)2006 Elsevier Inc.保留所有权利。
The addition of animal serum or specific protein growth factors to quiescent, serum-deprived vertebrate cells in culture activates a wide variety of biochemical responses within minutes, which are followed in 5-10h by the initiation of DNA synthesis and then by mitosis. The quintessential early and continuing activation step for the increase in DNA synthesis is the increased initiation rate of protein synthesis, which must be continuously maintained throughout the G1 phase for advancement into S. The aggregate of biochemical reactions to growth factors is called the coordinate response, to indicate that many related and unrelated processes are orchestrated to repetitively reproduce cells. It is, however, crucial to recognize that the coordinate response can be induced for one or more rounds of replication by a variety of non-specific and quasi-specific membrane effectors. The logic of considering this framework of events in growth control implied that a single multi-target second messenger plays a central role in coordinating the events of the overall response. The same reasoning suggested that free Mg2+ is the unifying regulatory element in that response which includes protein kinase pathways, and that the cytoplasmic activity of Mg2+ increases with the binding of growth factors to their receptors in the cell membrane, or of less specific perturbations of the membrane. Experimental support of this conclusion is presented here and is represented in the MMM model of cell proliferation control. (c) 2006 Elsevier Inc. All rights reserved.