RT Journal Article
SR Electronic
T1 Size uniformity of animal cells is actively maintained by a p38 MAPK-dependent regulation of G1-length
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 119867
DO 10.1101/119867
A1 Shixuan Liu
A1 Miriam B. Ginzberg
A1 Nish Patel
A1 Marc Hild
A1 Bosco Leung
A1 Yen-Chi Chen
A1 Zhengda Li
A1 Nancy Chang
A1 Shulamit Diena
A1 Yuan Wang
A1 William Trimble
A1 Larry Wasserman
A1 Jeremy Jenkins
A1 W. Kirschner Marc
A1 Ran Kafri
YR 2017
UL http://biorxiv.org/content/early/2017/03/23/119867.abstract
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.