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 Yoshida, K.
Right arrow Articles by Miki, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yoshida, K.
Right arrow Articles by Miki, Y.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2006, p. 3414-3431, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3414-3431.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Protein Kinase C {delta} Activates Topoisomerase II{alpha} To Induce Apoptotic Cell Death in Response to DNA Damage

Kiyotsugu Yoshida,1* Tomoko Yamaguchi,1 Hirokuni Shinagawa,1 Naoe Taira,1 Keiichi I. Nakayama,2 and Yoshio Miki1

Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan,1 Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan2

Received 17 January 2006/ Accepted 3 February 2006

DNA topoisomerase II is an essential nuclear enzyme that modulates DNA processes by altering the topological state of double-stranded DNA. This enzyme is required for chromosome condensation and segregation; however, the regulatory mechanism of its activation is largely unknown. Here we demonstrate that topoisomerase II{alpha} is activated in response to genotoxic stress. Concomitant with the activation, the expression of topoisomerase II{alpha} is increased following DNA damage. The results also demonstrate that the proapoptotic kinase protein kinase C {delta} (PKC{delta}) interacts with topoisomerase II{alpha}. This association is in an S-phase-specific manner and is required for stabilization and catalytic activation of topoisomerase II{alpha} in response to DNA damage. Conversely, inhibition of PKC{delta} activity attenuates DNA damage-induced activation of topoisomerase II{alpha}. Finally, aberrant activation of topoisomerase II{alpha} by PKC{delta} is associated with induction of apoptosis upon exposure to genotoxic agents. These findings indicate that PKC{delta} regulates topoisomerase II{alpha} and thereby cell fate in the genotoxic stress response.

* Corresponding author. Mailing address: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Phone: 81 3 5803 5826. Fax: 81 3 5803 0242. E-mail: yos.mgen{at}mri.tmd.ac.jp.

Molecular and Cellular Biology, May 2006, p. 3414-3431, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3414-3431.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kato, K., Yamanouchi, D., Esbona, K., Kamiya, K., Zhang, F., Kent, K. C., Liu, B. (2009). Caspase-mediated protein kinase C-{delta} cleavage is necessary for apoptosis of vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 297: H2253-H2261 [Abstract] [Full Text]  
  • Lu, Z.-G., Liu, H., Yamaguchi, T., Miki, Y., Yoshida, K. (2009). Protein Kinase C{delta} Activates RelA/p65 and Nuclear Factor-{kappa}B Signaling in Response to Tumor Necrosis Factor-{alpha}. Cancer Res. 69: 5927-5935 [Abstract] [Full Text]  
  • Wang, Y., Azuma, Y., Moore, D., Osheroff, N., Neufeld, K. L. (2008). Interaction between Tumor Suppressor Adenomatous Polyposis Coli and Topoisomerase II{alpha}: Implication for the G2/M Transition. Mol. Biol. Cell 19: 4076-4085 [Abstract] [Full Text]  
  • Liu, H., Lu, Z.-G., Miki, Y., Yoshida, K. (2007). Protein Kinase C {delta} Induces Transcription of the TP53 Tumor Suppressor Gene by Controlling Death-Promoting Factor Btf in the Apoptotic Response to DNA Damage. Mol. Cell. Biol. 27: 8480-8491 [Abstract] [Full Text]  
  • Yamaguchi, T., Kimura, J., Miki, Y., Yoshida, K. (2007). The Deubiquitinating Enzyme USP11 Controls an I{kappa}B Kinase {alpha} (IKK{alpha})-p53 Signaling Pathway in Response to Tumor Necrosis Factor {alpha} (TNF{alpha}). J. Biol. Chem. 282: 33943-33948 [Abstract] [Full Text]  
  • DeVries-Seimon, T. A., Ohm, A. M., Humphries, M. J., Reyland, M. E. (2007). Induction of Apoptosis Is Driven by Nuclear Retention of Protein Kinase C{delta}. J. Biol. Chem. 282: 22307-22314 [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»