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 Wang, Q.
Right arrow Articles by Dai, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, Q.
Right arrow Articles by Dai, W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2002, p. 3450-3459, Vol. 22, No. 10
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.10.3450-3459.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cell Cycle Arrest and Apoptosis Induced by Human Polo-Like Kinase 3 Is Mediated through Perturbation of Microtubule Integrity

Qi Wang,1 Suqing Xie,1 Jie Chen,2 Kenji Fukasawa,3 Ulhas Naik,4 Frank Traganos,1 Zbigniew Darzynkiewicz,1 Meena Jhanwar-Uniyal,2 and Wei Dai1*

Department of Medicine and Brander Cancer Research Institute, New York Medical College,1 American Health Foundation, Valhalla, New York 10595,2 Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45269,3 Department of Biological Sciences, University of Delaware, Newark, Delaware 197164

Received 31 July 2001/ Returned for modification 7 October 2001/ Accepted 5 February 2002

Human Polo-like kinase 3 (Plk3, previously termed Prk or Fnk) is involved in regulation of cell cycle progression through the M phase (B. Ouyang, H. Pan, L. Lu, J. Li, P. Stambrook, B. Li, and W. Dai, J. Biol. Chem. 272:28646-28651, 1997). Here we report that in most interphase cells endogenous Plk3 was predominantly localized around the nuclear membrane. Double labeling with Plk3 and {gamma}-tubulin, the latter a major component of pericentriole materials, revealed that Plk3 was closely associated with centrosomes and that its localization to centrosomes was dependent on the integrity of microtubules. Throughout mitosis, Plk3 appeared to be localized to mitotic apparatus such as spindle poles and mitotic spindles. During telophase, a significant amount of Plk3 was also detected in the midbody. Ectopic expression of Plk3 mutants dramatically changed cell morphology primarily due to their effects on microtubule dynamics. Expression of a constitutively active Plk3 (Plk3-A) resulted in rapid cell shrinkage, which led to formation of cells with an elongated, unsevered, and taxol-sensitive midbody. In contrast, cells expressing a kinase-defective Plk3 (Plk3K52R) mutant exhibited extended, deformed cytoplasmic structures, the phenotype of which was somewhat refractory to taxol treatment. Expression of both Plk3-A and Plk3K52R induced apparent G2/M arrest followed by apoptosis, although the kinase-defective mutant was less effective. Taken together, our studies strongly suggest that Plk3 plays an important role in the regulation of microtubule dynamics and centrosomal function in the cell and that deregulated expression of Plk3 results in cell cycle arrest and apoptosis.

* Corresponding author. Mailing address: Department of Medicine, New York Medical College, 4 Skyline Dr., Hawthorne, NY 10532. Phone: (914) 347-7452. Fax: (914) 345-2860. E-mail: wei_dai{at}nymc.edu.

Molecular and Cellular Biology, May 2002, p. 3450-3459, Vol. 22, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.10.3450-3459.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sang, M., Ando, K., Okoshi, R., Koida, N., Li, Y., Zhu, Y., Shimozato, O., Geng, C., Shan, B., Nakagawara, A., Ozaki, T. (2009). Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation. GENES CELLS 14: 775-788 [Abstract] [Full Text]  
  • Horner, T. J., Lai, W. S., Stumpo, D. J., Blackshear, P. J. (2009). Stimulation of Polo-Like Kinase 3 mRNA Decay by Tristetraprolin. Mol. Cell. Biol. 29: 1999-2010 [Abstract] [Full Text]  
  • Lopez-Sanchez, I., Sanz-Garcia, M., Lazo, P. A. (2009). Plk3 Interacts with and Specifically Phosphorylates VRK1 in Ser342, a Downstream Target in a Pathway That Induces Golgi Fragmentation. Mol. Cell. Biol. 29: 1189-1201 [Abstract] [Full Text]  
  • Wang, L., Gao, J., Dai, W., Lu, L. (2008). Activation of Polo-like Kinase 3 by Hypoxic Stresses. J. Biol. Chem. 283: 25928-25935 [Abstract] [Full Text]  
  • Yang, Y., Bai, J., Shen, R., Brown, S. A.N., Komissarova, E., Huang, Y., Jiang, N., Alberts, G. F., Costa, M., Lu, L., Winkles, J. A., Dai, W. (2008). Polo-like Kinase 3 Functions as a Tumor Suppressor and Is a Negative Regulator of Hypoxia-Inducible Factor-1{alpha} under Hypoxic Conditions. Cancer Res. 68: 4077-4085 [Abstract] [Full Text]  
  • Yang, F., Camp, D. G. II, Gritsenko, M. A., Luo, Q., Kelly, R. T., Clauss, T. R. W., Brinkley, W. R., Smith, R. D., Stenoien, D. L. (2007). Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus. J. Cell Sci. 120: 4060-4070 [Abstract] [Full Text]  
  • Wang, L., Dai, W., Lu, L. (2007). Stress-induced c-Jun Activation Mediated by Polo-like Kinase 3 in Corneal Epithelial Cells. J. Biol. Chem. 282: 32121-32127 [Abstract] [Full Text]  
  • Zimmerman, W. C., Erikson, R. L. (2007). Polo-like kinase 3 is required for entry into S phase. Proc. Natl. Acad. Sci. USA 104: 1847-1852 [Abstract] [Full Text]  
  • Liu, Y., Jiang, N., Wu, J., Dai, W., Rosenblum, J. S. (2007). Polo-like Kinases Inhibited by Wortmannin: LABELING SITE AND DOWNSTREAM EFFECTS. J. Biol. Chem. 282: 2505-2511 [Abstract] [Full Text]  
  • Dao, L. D., Duffy, A., Van Tine, B. A., Wu, S.-Y., Chiang, C.-M., Broker, T. R., Chow, L. T. (2006). Dynamic Localization of the Human Papillomavirus Type 11 Origin Binding Protein E2 through Mitosis While in Association with the Spindle Apparatus.. J. Virol. 80: 4792-4800 [Abstract] [Full Text]  
  • Jiang, N., Wang, X., Jhanwar-Uniyal, M., Darzynkiewicz, Z., Dai, W. (2006). Polo Box Domain of Plk3 Functions as a Centrosome Localization Signal, Overexpression of Which Causes Mitotic Arrest, Cytokinesis Defects, and Apoptosis. J. Biol. Chem. 281: 10577-10582 [Abstract] [Full Text]  
  • Jen, K.-Y., Cheung, V. G. (2005). Identification of Novel p53 Target Genes in Ionizing Radiation Response. Cancer Res. 65: 7666-7673 [Abstract] [Full Text]  
  • Li, Z., Niu, J., Uwagawa, T., Peng, B., Chiao, P. J. (2005). Function of Polo-like Kinase 3 in NF-{kappa}B-mediated Proapoptotic Response. J. Biol. Chem. 280: 16843-16850 [Abstract] [Full Text]  
  • Zhang, H., Shi, X., Paddon, H., Hampong, M., Dai, W., Pelech, S. (2004). B23/Nucleophosmin Serine 4 Phosphorylation Mediates Mitotic Functions of Polo-like Kinase 1. J. Biol. Chem. 279: 35726-35734 [Abstract] [Full Text]  
  • Verschuren, E. W., Jones, N., Evan, G. I. (2004). The cell cycle and how it is steered by Kaposi's sarcoma-associated herpesvirus cyclin. J. Gen. Virol. 85: 1347-1361 [Abstract] [Full Text]  
  • Wang, Q., Liu, T., Fang, Y., Xie, S., Huang, X., Mahmood, R., Ramaswamy, G., Sakamoto, K. M., Darzynkiewicz, Z., Xu, M., Dai, W. (2004). BUBR1 deficiency results in abnormal megakaryopoiesis. Blood 103: 1278-1285 [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»