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Molecular Biology, Pathobiology, and Genetics |
Hormel Institute, University of Minnesota, Austin, Minnesota
Requests for reprints: Zigang Dong, Hormel Institute, University of Minnesota, 801 16th Avenue Northeast, Austin, MN 55912. Phone: 507-437-9600; Fax: 507-437-9606; E-mail: zgdong{at}hi.umn.edu.
The tumor suppressor p53 protein is one of the most highly connected nodes in cellular signal transduction pathways and acts as a central regulatory switch in networks controlling cell proliferation and apoptosis. It is involved in the activation of genes that maintain control over cellular responses to DNA errors such as DNA repair, chromosomal recombination, and chromosome segregation. Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus. Deficiency of p53 diminishes RSK2-mediated phosphorylation of histone H3 (Ser10) and adding back p53 to p53–/– embryonic fibroblasts restored phosphorylation of histone H3 at Ser10. These results show that the p53 protein is an important substrate of RSK2 and a critical intermediary in the RSK2 and histone H3 interaction. The RSK2-p53-histone H3 complex may likely contribute to chromatin remodeling and cell cycle regulation.
This article has been cited by other articles:
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  S. Llanos, A. Cuadrado, and M. Serrano MSK2 Inhibits p53 Activity in the Absence of Stress Sci. Signal., September 22, 2009; 2(89): ra57 - ra57. [Abstract] [Full Text] [PDF]
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 Y.-Y. Cho, K. Yao, A. Pugliese, M. L. Malakhova, A. M. Bode, and Z. Dong A Regulatory Mechanism for RSK2 NH2-Terminal Kinase Activity Cancer Res., May 15, 2009; 69(10): 4398 - 4406. [Abstract] [Full Text] [PDF]
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D. Zheng, Y.-Y. Cho, A. T.Y. Lau, J. Zhang, W.-Y. Ma, A. M. Bode, and Z. Dong Cyclin-Dependent Kinase 3-Mediated Activating Transcription Factor 1 Phosphorylation Enhances Cell Transformation Cancer Res., September 15, 2008; 68(18): 7650 - 7660. [Abstract] [Full Text] [PDF]
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Y.-Y. Cho, K. Yao, H.-G. Kim, B. S. Kang, D. Zheng, A. M. Bode, and Z. Dong Ribosomal S6 Kinase 2 Is a Key Regulator in Tumor Promoter Induced Cell Transformation Cancer Res., September 1, 2007; 67(17): 8104 - 8112. [Abstract] [Full Text] [PDF]
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S.-M. Oh, F. Zhu, Y.-Y. Cho, K. W. Lee, B. S. Kang, H.-G. Kim, T. Zykova, A. M. Bode, and Z. Dong T-Lymphokine-Activated Killer Cell-Originated Protein Kinase Functions as a Positive Regulator of c-Jun-NH2-Kinase 1 Signaling and H-Ras-Induced Cell Transformation Cancer Res., June 1, 2007; 67(11): 5186 - 5194. [Abstract] [Full Text] [PDF]
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 Y.-Y. Cho, K. Yao, A. M. Bode, H. R. Bergen III, B. J. Madden, S.-M. Oh, S. Ermakova, B. S. Kang, H. S. Choi, J.-H. Shim, et al. RSK2 Mediates Muscle Cell Differentiation through Regulation of NFAT3 J. Biol. Chem., March 16, 2007; 282(11): 8380 - 8392. [Abstract] [Full Text] [PDF]
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 M. Falco, C. Romano, A. Alberti, D. Greco, C. Scuderi, E. Avola, P. Failla, S. Belli, J. L. Tolmie, S. Amata, et al. Identification of Novel Mutations in Patients with Coffin-Lowry Syndrome by a Denaturing HPLC-Based Assay Clin. Chem., December 1, 2005; 51(12): 2356 - 2358. [Full Text] [PDF]
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