The p38-Mediated Stress-Activated Checkpoint: A Rapid Response System for Delaying Progression through Antephase and Entry into Mitosis
Volume 4, Issue 1
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Pages 57 - 62http://dx.doi.org/10.4161/cc.4.1.1357
Authors: Alexei Mikhailov, Mio Shinohara and Conly L. Rieder View affiliations
Cells have evolved a number of control pathways that delay or prevent them from entering mitosis under conditions that can compromise genome integrity. One recently appreciated and versatile control pathway involves the p38 stress activated protein kinase. During late G2 p38 is rapidly activated by diverse stresses (topoisomerase II (topo II)) and histone deacetylase inhibitors, osmotic shock, microtubule disassembly, UV light, etc) via a number of different pathways. Once activated p38 appears to delay entry into mitosis by inhibiting cdc25B phosphatase that, in turn, downregulates cyclin A/CDK2 activity. Depending on the agent and degree of stress, this delay may be transient, or it may last until transcription mediated checkpoint pathways can take over.