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Protein phosphatase 2A has an essential role in the activation of γ-irradiation-induced G2/M checkpoint response

Oncogene volume 29, pages 4317–4329 (2010)Cite this article

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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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  1. P T Cao and P M Greer: These authors contributed equally to this work.

Authors and Affiliations

  1. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA

    Y Yan, P T Cao, P M Greer, E S Nagengast, R H Kolb & K H Cowan

  2. Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

    M C Mumby

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  1. Y Yan
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Correspondence to K H Cowan.

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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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