Martinsson Hanna-Stina, Zickert Peter, Starborg Maria, Larsson Olle, Zetterberg Anders
Karolinska Institutet, Department of Oncology-Pathology, Karolinska Hospital/CCK R8:04, Stockholm, Sweden.
J Cell Physiol. 2005 Apr;203(1):27-34. doi: 10.1002/jcp.20204.
The restriction point (R) separates the G1 phase of continuously cycling cells into two functionally different parts. The first part, G1-pm, represents the growth factor dependent post-mitotic interval from mitosis to R, which is of constant length (3-4 h). The second part, G1-ps, represents the growth factor independent, pre-S phase interval of G1 that lasts from R to S and that varies in time from 1 to 10 h. G1-pm cells rapidly exit (within 1 h) from the cell cycle and enter G0 as a response to serum withdrawal. The finding that R occurs at a set time after mitosis indicates that R may be related to the metabolic and/or structural changes that the cell underwent during the previous mitosis. We have recently shown that phosphorylation of the retinoblastoma tumor suppressor protein (pRb) is not the molecular mechanism behind R, as has been suggested previously. Here, we present an alternative explanation for R. In the present study, we applied a single cell approach using time-lapse analysis, which revealed that upon serum starvation the G1-pm cells rapidly underwent a transient change in cell shape from flat to spherical before exiting to G0. Platelet derived growth factor (PDGF) counteracted this change in shape and also prevented exit to G0 to the same extent. Furthermore epidermal growth factor (EGF) and insulin like growth factor (IGF-1), which only partially counteracted this change, only partially counteracts exit to G0. These data clearly indicate a direct link between change in cell shape and exit to G0 in G1-cells that have not passed R.
限制点（R）将持续循环细胞的G1期分为两个功能不同的部分。第一部分，G1-pm，代表从有丝分裂到R的依赖生长因子的有丝分裂后间隔期，其长度恒定（3 - 4小时）。第二部分，G1-ps，代表G1期独立于生长因子的S期前间隔期，从R持续到S，时间从1到10小时不等。G1-pm细胞在血清剥夺后1小时内迅速退出细胞周期并进入G0期。R在有丝分裂后特定时间出现这一发现表明，R可能与细胞在前一次有丝分裂期间经历的代谢和/或结构变化有关。我们最近发现，视网膜母细胞瘤肿瘤抑制蛋白（pRb）的磷酸化并非如先前所认为的那样是R背后的分子机制。在此，我们提出对R的另一种解释。在本研究中，我们采用了一种使用延时分析的单细胞方法，结果显示血清饥饿时，G1-pm细胞在退出至G0期之前迅速经历了从扁平到球形的短暂细胞形态变化。血小板衍生生长因子（PDGF）抵消了这种形态变化，并且在相同程度上也阻止了细胞退出至G0期。此外，表皮生长因子（EGF）和胰岛素样生长因子（IGF-1）仅部分抵消了这种变化，也仅部分抵消了细胞退出至G0期。这些数据清楚地表明，在未通过R的G1期细胞中，细胞形态变化与退出至G0期之间存在直接联系。
