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Akt2, but not Akt1, is required for cell survival by inhibiting activation of JNK and p38 after UV irradiation

Oncogene volume 28, pages 1241–1247 (2009)Cite this article

Abstract

The serine/threonine protein kinase, Akt/PKB, has an essential function in cell survival during response to various stresses. Recent studies have demonstrated that Akt isoforms exhibit some distinct physiological functions, but the isotype-specific functions for Akt in the stress response have not been fully identified. In this study, we analysed the cellular response to genotoxic stress using isogenic wild-type, Akt1−/− and Akt2−/− mouse embryonic fibroblasts (MEFs). Marked hypersensitivity of Akt2−/− MEFs was observed to UV irradiation, whereas wild-type and Akt1−/− MEFs showed comparable levels of resistance. Akt2−/− mouse aortic endothelial cells also showed hypersensitivity to UV and the reconstitution of Akt2 expression in the Akt2−/− MEFs restored the UV resistance of the cells. Interestingly, upon UV irradiation, JNK and p38 were significantly upregulated in Akt2−/− MEFs, compared to wild-type and Akt1−/− MEFs. Additionally, inhibition of JNK and p38 activation reduced UV-induced cell death. Furthermore, both the hyperactivation of JNK and p38 and the UV-induced cell death in Akt2−/− MEFs were completely inhibited by restoring Akt2 expression. These results indicate that Akt2, but not Akt1, is essential for cell survival upon UV irradiation, and that Akt2 prevents UV-induced cell death by inhibiting activation of JNK and p38.

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Acknowledgements

This work was supported by a grant of the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0620060-2) and Research Program of dual regulation mechanisms of aging and cancer from KOSEF (Korea Science and Engineering Foundation) (M1075604000107N560400110).

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  1. M-A Kim and H-J Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, Dong-A University, Busan, South Korea

    M-A Kim, H-J Kim, H J Jee, A J Kim, Y-S Bae & J Yun

  2. Department of Pharmacology, College of Medicine, Pusan University, Busan, South Korea

    S S Bae

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  1. M-A Kim
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Correspondence to J Yun.

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Kim, MA., Kim, HJ., Jee, H. et al. Akt2, but not Akt1, is required for cell survival by inhibiting activation of JNK and p38 after UV irradiation. Oncogene 28, 1241–1247 (2009). https://doi.org/10.1038/onc.2008.487

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