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

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 iden...

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Detalles Bibliográficos
Autores principales: Liu, Shixuan, Ginzberg, Miriam Bracha, Patel, Nish, Hild, Marc, Leung, Bosco, Li, Zhengda, Chen, Yen-Chi, Chang, Nancy, Wang, Yuan, Tan, Ceryl, Diena, Shulamit, Trimble, William, Wasserman, Larry, Jenkins, Jeremy L, Kirschner, Marc W, Kafri, Ran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876018/
https://www.ncbi.nlm.nih.gov/pubmed/29595474
http://dx.doi.org/10.7554/eLife.26947
Descripción
Sumario: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.