Size uniformity of animal cells is actively maintained by a p38 MAPK-dependent regulation of G1-length

Author:

Liu Shixuan12,Ginzberg Miriam Bracha1,Patel Nish1,Hild Marc3,Leung Bosco1,Li Zhengda4,Chen Yen-Chi5ORCID,Chang Nancy1,Wang Yuan3,Tan Ceryl12,Diena Shulamit12,Trimble William1,Wasserman Larry6,Jenkins Jeremy L3,Kirschner Marc W7ORCID,Kafri Ran12ORCID

Affiliation:

1. Cell Biology Program, The Hospital for Sick Children, Toronto, Canada

2. Department of Molecular Genetics, University of Toronto, Toronto, Canada

3. Novartis Institutes for BioMedical Research, Cambridge, United States

4. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States

5. Department of Statistics, University of Washington, Seattle, United States

6. Department of Statistics, Carnegie Mellon University, Pittsburgh, United States

7. Department of Systems Biology, Harvard Medical School, Boston, United States

Abstract

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.

Funder

Canadian Institutes of Health Research

National Institute of General Medical Sciences

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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