Abstract
G2/M checkpoint activation after DNA damage results in G2/M cell cycle arrest that allows time for DNA repair before the entry of cells into mitosis. Activation of G2/M checkpoint involves a series of signaling events, which include activation of ataxia telangiectecia-mutated and Rad3-related (ATR) and Chk1 kinases and inhibition of Cdc2/Cyclin B activity. Studies presented in this report show that serine (Ser)/threonine (Thr) protein phosphatase 2A (PP2A) has an important role in G2/M checkpoint activation in response to γ-irradiation (IR) exposure. Using PP2A inhibitors, as well as siRNA targeting various forms of Ser/Thr protein phosphatases, results presented in this report show that specific PP2A inhibition abrogates IR-induced activation of ATR and Chk1 kinases, as well as phosphorylation of Cdc2-Tyr15, and attenuates IR-induced G2/M arrest. These results suggest an important regulation of PP2A on IR-induced G2/M checkpoint signaling response.
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Acknowledgements
We thank Dr Michel Ouellette for providing HPNE cells, Dr Helen Piwnica Worms for GST-Cdc25C construct, Dr Charles Kuzynski, Victoria Smith and Megan Michalak for assistance on the flow cytometry analysis, and Dr Janina Baranowska-Kortylewicz for assistance on the operation of Mark I 68A Cesium-137 Irradiator. This work was supported by Nebraska DHHS-LB506 grant 2007-45 to YY, NCI Training Grant (NCI T32 CA009476) to RK and NCI Cancer Center Support Grant (P30CA036727) to KC.
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Yan, Y., Cao, P., Greer, P. et al. Protein phosphatase 2A has an essential role in the activation of γ-irradiation-induced G2/M checkpoint response. Oncogene 29, 4317–4329 (2010). https://doi.org/10.1038/onc.2010.187
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DOI: https://doi.org/10.1038/onc.2010.187
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