This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Burns, T. F.
Right arrow Articles by El-Deiry, W. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Burns, T. F.
Right arrow Articles by El-Deiry, W. S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2003, p. 5556-5571, Vol. 23, No. 16
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.16.5556-5571.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Silencing of the Novel p53 Target Gene Snk/Plk2 Leads to Mitotic Catastrophe in Paclitaxel (Taxol)-Exposed Cells

Timothy F. Burns, Peiwen Fei, Kimberly A. Scata, David T. Dicker, and Wafik S. El-Deiry*

Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Departments of Medicine, Genetics, and Pharmacology and Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 11 February 2003/ Returned for modification 14 March 2003/ Accepted 22 May 2003

Loss of p53 sensitizes to antimicrotubule agents in human tumor cells, but little is known about its role during mitosis. We have identified the Polo-like kinase family member serum inducible kinase (Snk/Plk2) as a novel p53 target gene. Snk/Plk2 mutagenesis demonstrated that its kinase activity is negatively regulated by its C terminus. Small interfering RNA (siRNA)-mediated Snk/Plk2 silencing in the presence of the mitotic poisons paclitaxel (Taxol) or nocodazole significantly increased apoptosis, similar to p53 mutations, which confer paclitaxel sensitivity. Furthermore, we have demonstrated that the apoptosis due to silencing of Snk/Plk2 in the face of spindle damage occurs in mitotic cells and not in cells that have progressed to a G1-like state without dividing. Since siRNA directed against Snk/Plk2 promoted death of paclitaxel-treated cells in mitosis, we envision a mitotic checkpoint wherein p53-dependent activation of Snk/Plk2 prevents mitotic catastrophe following spindle damage. Finally, these studies suggest that disruption of Snk/Plk2 may be of therapeutic value in sensitizing paclitaxel-resistant tumors.

* Corresponding author. Mailing address: HHMI, University of Pennsylvania, 415 Curie Blvd., CRB 437A, Philadelphia, PA 19104. Phone: (215) 898-9015. Fax: (215) 573-9139. E-mail: wafik{at}mail.med.upenn.edu.

Molecular and Cellular Biology, August 2003, p. 5556-5571, Vol. 23, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.16.5556-5571.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, B., Xiao, Z., Ren, E. C. (2009). Redefining the p53 response element. Proc. Natl. Acad. Sci. USA 106: 14373-14378 [Abstract] [Full Text]  
  • Matsumoto, T., Wang, P.-y., Ma, W., Sung, H. J., Matoba, S., Hwang, P. M. (2009). Polo-like kinases mediate cell survival in mitochondrial dysfunction. Proc. Natl. Acad. Sci. USA 106: 14542-14546 [Abstract] [Full Text]  
  • Rudolph, D., Steegmaier, M., Hoffmann, M., Grauert, M., Baum, A., Quant, J., Haslinger, C., Garin-Chesa, P., Adolf, G. R. (2009). BI 6727, A Polo-like Kinase Inhibitor with Improved Pharmacokinetic Profile and Broad Antitumor Activity. Clin. Cancer Res. 15: 3094-3102 [Abstract] [Full Text]  
  • Li, Z., Lu, J., Sun, M., Mi, S., Zhang, H., Luo, R. T., Chen, P., Wang, Y., Yan, M., Qian, Z., Neilly, M. B., Jin, J., Zhang, Y., Bohlander, S. K., Zhang, D.-E., Larson, R. A., Le Beau, M. M., Thirman, M. J., Golub, T. R., Rowley, J. D., Chen, J. (2008). Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc. Natl. Acad. Sci. USA 105: 15535-15540 [Abstract] [Full Text]  
  • Schmit, T. L, Ahmad, N. (2008). Regulation of Mitosis via Mitotic Kinases: New Opportunities for Cancer Management. aacredbook 2008: 133-150 [Abstract] [Full Text]  
  • Niikura, Y., Dixit, A., Scott, R., Perkins, G., Kitagawa, K. (2007). BUB1 mediation of caspase-independent mitotic death determines cell fate. JCB 178: 283-296 [Abstract] [Full Text]  
  • Schmit, T. L., Ahmad, N. (2007). Regulation of mitosis via mitotic kinases: new opportunities for cancer management. Molecular Cancer Therapeutics 6: 1920-1931 [Abstract] [Full Text]  
  • Eickhoff, M., Thalmann, J., Hess, S., Martin, M., Laue, T., Kruppa, J., Brandes, G., Klos, A. (2007). Host Cell Responses to Chlamydia pneumoniae in Gamma Interferon-Induced Persistence Overlap Those of Productive Infection and Are Linked to Genes Involved in Apoptosis, Cell Cycle, and Metabolism. Infect. Immun. 75: 2853-2863 [Abstract] [Full Text]  
  • Kim, J.-S., Lee, C., Bonifant, C. L., Ressom, H., Waldman, T. (2007). Activation of p53-Dependent Growth Suppression in Human Cells by Mutations in PTEN or PIK3CA. Mol. Cell. Biol. 27: 662-677 [Abstract] [Full Text]  
  • Leao, M., Anderton, E., Wade, M., Meekings, K., Allday, M. J. (2007). Epstein-Barr Virus-Induced Resistance to Drugs That Activate the Mitotic Spindle Assembly Checkpoint in Burkitt's Lymphoma Cells. J. Virol. 81: 248-260 [Abstract] [Full Text]  
  • Wang, S., El-Deiry, W. S. (2006). p73 or p53 Directly Regulates Human p53 Transcription to Maintain Cell Cycle Checkpoints.. Cancer Res. 66: 6982-6989 [Abstract] [Full Text]  
  • Bhonde, M. R., Hanski, M.-L., Budczies, J., Cao, M., Gillissen, B., Moorthy, D., Simonetta, F., Scherubl, H., Truss, M., Hagemeier, C., Mewes, H.-W., Daniel, P. T., Zeitz, M., Hanski, C. (2006). DNA Damage-induced Expression of p53 Suppresses Mitotic Checkpoint Kinase hMps1: THE LACK OF THIS SUPPRESSION IN p53MUT CELLS CONTRIBUTES TO APOPTOSIS. J. Biol. Chem. 281: 8675-8685 [Abstract] [Full Text]  
  • Dijkhuis, A.-J., Klappe, K., Jacobs, S., Kroesen, B.-J., Kamps, W., Sietsma, H., Kok, J. W. (2006). PDMP sensitizes neuroblastoma to paclitaxel by inducing aberrant cell cycle progression leading to hyperploidy.. Molecular Cancer Therapeutics 5: 593-601 [Abstract] [Full Text]  
  • Syed, N., Smith, P., Sullivan, A., Spender, L. C., Dyer, M., Karran, L., O'Nions, J., Allday, M., Hoffmann, I., Crawford, D., Griffin, B., Farrell, P. J., Crook, T. (2006). Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies. Blood 107: 250-256 [Abstract] [Full Text]  
  • Zyss, D., Montcourrier, P., Vidal, B., Anguille, C., Merezegue, F., Sahuquet, A., Mangeat, P. H., Coopman, P. J. (2005). The Syk Tyrosine Kinase Localizes to the Centrosomes and Negatively Affects Mitotic Progression. Cancer Res. 65: 10872-10880 [Abstract] [Full Text]  
  • Hirose, Y., Katayama, M., Mirzoeva, O. K., Berger, M. S., Pieper, R. O. (2005). Akt Activation Suppresses Chk2-Mediated, Methylating Agent-Induced G2 Arrest and Protects from Temozolomide-Induced Mitotic Catastrophe and Cellular Senescence. Cancer Res. 65: 4861-4869 [Abstract] [Full Text]  
  • van de Weerdt, B. C. M., van Vugt, M. A. T. M., Lindon, C., Kauw, J. J. W., Rozendaal, M. J., Klompmaker, R., Wolthuis, R. M. F., Medema, R. H. (2005). Uncoupling Anaphase-Promoting Complex/Cyclosome Activity from Spindle Assembly Checkpoint Control by Deregulating Polo-Like Kinase 1. Mol. Cell. Biol. 25: 2031-2044 [Abstract] [Full Text]  
  • Einarson, M. B., Cukierman, E., Compton, D. A., Golemis, E. A. (2004). Human Enhancer of Invasion-Cluster, a Coiled-Coil Protein Required for Passage through Mitosis. Mol. Cell. Biol. 24: 3957-3971 [Abstract] [Full Text]  
  • Wu, W., Hodges, E., Redelius, J., Hoog, C. (2004). A novel approach for evaluating the efficiency of siRNAs on protein levels in cultured cells. Nucleic Acids Res 32: e17-e17 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»