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RSK promotes G2/M transition through activating phosphorylation of Cdc25A and Cdc25B

Oncogene volume 33, pages 2385–2394 (2014)Cite this article

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Abstract

Activation of the mitogen-activated protein kinase (MAPK) cascade in mammalian cell lines positively regulates the G2/M transition. The molecular mechanism underlying this biological phenomenon remains poorly understood. Ribosomal S6 kinase (RSK) is a key downstream element of the MAPK cascade. Our previous studies established roles of RSK2 in Cdc25C activation during progesterone-induced meiotic maturation of Xenopus oocytes. In this study we demonstrate that both recombinant RSK and endogenous RSK in Xenopus egg extracts phosphorylate all three isoforms of human Cdc25 at a conserved motif near the catalytic domain. In human HEK293 and PC-3mm2 cell lines, RSK preferentially phosphorylates Cdc25A and Cdc25B in mitotic cells. Phosphorylation of the RSK sites in these Cdc25 isoforms increases their M-phase-inducing activities. Inhibition of RSK-mediated phosphorylation of Cdc25 inhibits G2/M transition. Moreover, RSK is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of T359/S363 in RSK. Together, these findings indicate that RSK promotes G2/M transition in mammalian cells through activating phosphorylation of Cdc25A and Cdc25B.

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Acknowledgements

This work was supported by the Department of Defense (DOD) Prostate Cancer Research Program (PCRP) grants W81XWH-09-1-0274 (JK) and W81XWH-09-1-0272 (S-HL), by grant 30300173 from the National Natural Science Foundation of China and grant 20071D0503100293 from the Beijing Talents Foundation (WZ), and a PCF Challenge grant and NCI CA140388 (GEG). DNA sequencing was performed by the DNA Analysis Facility of UT MD Anderson Cancer Center supported by NCI grant CA 16672. The Translational Chemistry Core Facility at the MD Anderson Cancer Center was supported by the Cancer Center support grant CA016672.

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  1. C F Wu and S Liu: These authors are the co-first authors.

Authors and Affiliations

  1. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    C F Wu, R Wang, S Sun, W G Bornmann & J Kuang

  2. The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China

    S Liu, F Yin & W Zhang

  3. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Y-C Lee & S-H Lin

  4. The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA

    S Sun, G E Gallick, S-H Lin & J Kuang

  5. Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    L-Y Yu-Lee

  6. Department of Genitourinary Medical Oncology Research, David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    G E Gallick

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Wu, C., Liu, S., Lee, YC. et al. RSK promotes G2/M transition through activating phosphorylation of Cdc25A and Cdc25B. Oncogene 33, 2385–2394 (2014). https://doi.org/10.1038/onc.2013.182

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