PT  - JOURNAL ARTICLE
AU  - Shixuan Liu
AU  - Miriam B. Ginzberg
AU  - Nish Patel
AU  - Marc Hild
AU  - Bosco Leung
AU  - Yen-Chi Chen
AU  - Zhengda Li
AU  - Nancy Chang
AU  - Shulamit Diena
AU  - Yuan Wang
AU  - William Trimble
AU  - Larry Wasserman
AU  - Jeremy Jenkins
AU  - W. Kirschner Marc
AU  - Ran Kafri
TI  - Size uniformity of animal cells is actively maintained by a p38 MAPK-dependent regulation of G1-length
AID  - 10.1101/119867
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 119867
4099  - http://biorxiv.org/content/early/2017/03/23/119867.short
4100  - http://biorxiv.org/content/early/2017/03/23/119867.full
AB  - 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.One-sentence summary The p38 MAP kinase pathway coordinates cell growth and cell cycle progression by lengthening G1 in small cells, allowing them more time to grow before their next division.