Magnesium: The missing element in molecular views of cell proliferation control.
Magnesium: The missing element in molecular views of cell proliferation control.
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DOI：
10.1002/bies.20183
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发表时间：
2005-03
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影响因子：
--
通讯作者：
H. Rubin
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文献类型：
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作者：
H. Rubin
细胞生长和增殖调控的定量研究始于 20 世纪 60 年代末脊椎动物细胞单层培养技术的发展。基本参数是在早期的生理研究中定义的，并持续了接下来的十年。其中包括特异性和非特异性生长因子，以及在 G1 期的大部分时间持续暴露于这些因子以进展到 S 的要求。在这项工作的过程中，阐明了生化反应的多样性以及增加蛋白质合成和积累对于 DNA 合成开始的关键作用。特别是，游离胞质 Mg2+ 在直接调节蛋白质合成和响应膜扰动的辅助过程中发挥着核心作用。最终，生理时代被 20 世纪 80 年代开始的分子时代所取代。这项工作的重点是生长因子的特定受体，这些受体夹带蛋白激酶级联，该级联以更高频率的蛋白质合成起始终止。然而，分子研究实际上忽略了生理时代的关键结果。然而，最近对蛋白质合成调节途径中倒数第二个分子步骤的研究支持了涉及膜扰动和 MgATP2 浓度的生长调节模型，其结果整合了生理学和分子时代的发现。由此产生的相对简单的增殖控制“膜、镁有丝分裂”（MMM）模型可以解释由质膜介导的各种特异性和非特异性生长促进治疗的看似矛盾的现象，这些治疗带来共同的、复杂但协调的生长反应，从而驱动细胞增殖。
The quantitative study of regulation of cell growth and proliferation began with the development of the technique for monolayer culture of vertebrate cells in the late 1960s. The basic parameters were defined in the early physiological studies, which continued through the next decade. These included specific and non-specific growth factors and the requirement for continuous exposure to such factors through most of the G1 period for progression to S. In the course of this work, the diversity of biochemical responses and the critical role of increased protein synthesis and accumulation for the onset of DNA synthesis were elucidated. In particular, a central role of free cytosolic Mg2+ in direct regulation of protein synthesis and in ancillary processes as a response to membrane perturbation was established. Eventually, the physiological era was superseded by the molecular era beginning in the 1980s. This work focussed on specific receptors for growth factors that entrained a protein kinase cascade, which terminated in a higher frequency of initiation of protein synthesis. However, the molecular studies virtually ignored the key results of the physiological era. Recent studies of the penultimate molecular steps in the regulatory pathway of protein synthesis, however, have supported a model of growth regulation involving membrane perturbation and MgATP2- concentration, results that integrate the findings of the physiological and molecular eras. The resulting relatively simple "membrane, magnesium mitosis" (MMM) model of proliferation control can explain the seeming paradox of the variety of specific and non-specific growth-enhancing treatments that are mediated by the plasma membrane and which bring about a shared, complex but coordinated growth response that drives cell proliferation.