Cell Biology Program, The Hospital for Sick Children, Toronto, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Canada.
Elife. 2018 Mar 29;7:e26947. doi: 10.7554/eLife.26947.
Animal cells within a tissue typically display a striking regularity in their size. To date, the molecular mechanisms that control this uniformity are still unknown. We have previously shown that size uniformity in animal cells is promoted, in part, by size-dependent regulation of G1 length. To identify the molecular mechanisms underlying this process, we performed a large-scale small molecule screen and found that the p38 MAPK pathway is involved in coordinating cell size and cell cycle progression. Small cells display higher p38 activity and spend more time in G1 than larger cells. Inhibition of p38 MAPK leads to loss of the compensatory G1 length extension in small cells, resulting in faster proliferation, smaller cell size and increased size heterogeneity. We propose a model wherein the p38 pathway responds to changes in cell size and regulates G1 exit accordingly, to increase cell size uniformity.
组织中的动物细胞通常在大小上表现出惊人的规律性。迄今为止，控制这种均匀性的分子机制仍不清楚。我们之前已经表明，动物细胞大小的均匀性部分是通过 G1 长度的大小依赖性调节来促进的。为了确定这一过程的分子机制，我们进行了大规模的小分子筛选，发现 p38 MAPK 途径参与协调细胞大小和细胞周期进程。小细胞显示出更高的 p38 活性，并且比大细胞花费更多的时间处于 G1 期。抑制 p38 MAPK 会导致小细胞中补偿性 G1 长度延长的丧失，从而导致更快的增殖、更小的细胞大小和增加的大小异质性。我们提出了一个模型，其中 p38 途径响应细胞大小的变化并相应地调节 G1 退出，以增加细胞大小的均匀性。
