The Apparent Requirement for Protein Synthesis during G2 Phase Is due to Checkpoint Activation

Autor: Sarah Lockhead, Alisa Moskaleva, Julia Kamenz, Yuxin Chen, Minjung Kang, Anay R. Reddy, Silvia D.M. Santos, James E. Ferrell, Jr.
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Reports, Vol 32, Iss 2, Pp 107901- (2020)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2020.107901
Popis: Summary: Protein synthesis inhibitors (e.g., cycloheximide) block mitotic entry, suggesting that cell cycle progression requires protein synthesis until right before mitosis. However, cycloheximide is also known to activate p38 mitogen-activated protein kinase (MAPK), which can delay mitotic entry through a G2/M checkpoint. Here, we ask whether checkpoint activation or a requirement for protein synthesis is responsible for the cycloheximide effect. We find that p38 inhibitors prevent cycloheximide-treated cells from arresting in G2 phase and that G2 duration is normal in approximately half of these cells. The Wee1 inhibitor MK-1775 and Wee1/Myt1 inhibitor PD0166285 also prevent cycloheximide from blocking mitotic entry, raising the possibility that Wee1 and/or Myt1 mediate the cycloheximide-induced G2 arrest. Thus, protein synthesis during G2 phase is not required for mitotic entry, at least when the p38 checkpoint pathway is abrogated. However, M phase progression is delayed in cycloheximide-plus-kinase-inhibitor-treated cells, emphasizing the different requirements of protein synthesis for timely entry and completion of mitosis.
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