Brooks Robert F
Molecular and Clinical Sciences Research Institute, St George's, University of London, London, United Kingdom.
Department of Anatomy, King's College London, London, United Kingdom.
Front Cell Dev Biol. 2021 Jul 23;9:698066. doi: 10.3389/fcell.2021.698066. eCollection 2021.
Exit of cells from quiescence following mitogenic stimulation is highly asynchronous, and there is a great deal of heterogeneity in the response. Even in a single, clonal population, some cells re-enter the cell cycle after a sub-optimal mitogenic signal while other, seemingly identical cells, do not, though they remain capable of responding to a higher level of stimulus. This review will consider the origins of this variability and heterogeneity, both in cells re-entering the cycle from quiescence and in the context of commitment decisions in continuously cycling populations. Particular attention will be paid to the role of two interacting molecular networks, namely the RB-E2F and APC/C "switches." These networks have the property of bistability and it seems likely that they are responsible for dynamic behavior previously described kinetically by Transition Probability models of the cell cycle. The relationship between these switches and the so-called Restriction Point of the cell cycle will also be considered.
有丝分裂原刺激后细胞从静止状态退出的过程是高度异步的，并且反应存在很大的异质性。即使在单个克隆群体中，一些细胞在次优有丝分裂原信号后重新进入细胞周期，而其他看似相同的细胞则不会，尽管它们仍然能够对更高水平的刺激做出反应。本综述将探讨这种变异性和异质性的起源，包括从静止状态重新进入细胞周期的细胞，以及连续循环群体中承诺决定的背景。将特别关注两个相互作用的分子网络，即RB-E2F和APC/C“开关”的作用。这些网络具有双稳态特性，似乎它们负责先前由细胞周期转换概率模型动力学描述的动态行为。还将考虑这些开关与细胞周期所谓的限制点之间的关系。
