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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Kamada, S.
Right arrow Articles by Hunter, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kamada, S.
Right arrow Articles by Hunter, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2005, p. 9469-9477, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9469-9477.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A-Kinase-Anchoring Protein 95 Functions as a Potential Carrier for the Nuclear Translocation of Active Caspase 3 through an Enzyme-Substrate-Like Association

Shinji Kamada,1,2,3* Ushio Kikkawa,2 Yoshihide Tsujimoto,3 and Tony Hunter1*

Molecular and Cell Biology Laboratory, The Salk Institute, La Jolla, California,1 Biosignal Research Center, Kobe University, Kobe, Japan,2 Laboratory of Molecular Genetics, Osaka University Medical School and Graduate School of Medicine, Suita, Osaka, Japan3

Received 29 June 2005/ Accepted 5 August 2005

Caspase-mediated proteolysis is a critical and central element of the apoptotic process, and caspase 3, one of the effector caspases, is proposed to play essential roles in the nuclear morphological changes of apoptotic cells. Although many substrates for caspase 3 localize in the nucleus and caspase 3 translocates from the cytoplasm to the nuclei after activation in apoptotic cells, the molecular mechanisms of nuclear translocation of active caspase 3 have been unclear. Recently, we suggested that a substrate-like protein(s) served as a carrier to transport caspase 3 from the cytoplasm into the nucleus. In the present study, we identified A-kinase-anchoring protein 95 (AKAP95) as a caspase 3-binding protein. Small interfering RNA-mediated depletion of AKAP95 reduced apoptotic nuclear morphological changes, suggesting that AKAP95 is involved in the process of apoptotic nuclear morphological changes. The association of AKAP95 with active caspase 3 was analogous to an enzyme-substrate interaction. Furthermore, overexpression of AKAP95 with nuclear localization sequence mutations inhibited nuclear morphological changes in apoptotic cells. These results indicate that AKAP95 is a potential carrier protein for active caspase 3 from the cytoplasm into the nuclei in apoptotic cells.

* Corresponding author. Mailing address for Shinji Kamada: Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan. Phone: 81-78-803-5965. Fax: 81-78-803-5972. E-mail: skamada{at}kobe-u.ac.jp. Mailing address for Tony Hunter: Molecular and Cell Biology Laboratory, The Salk Institute, 10010 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 453-4100. Fax: (858) 457-4765. E-mail: hunter{at}salk.edu.

Molecular and Cellular Biology, November 2005, p. 9469-9477, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9469-9477.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wall, E. A., Zavzavadjian, J. R., Chang, M. S., Randhawa, B., Zhu, X., Hsueh, R. C., Liu, J., Driver, A., Bao, X. R., Sternweis, P. C., Simon, M. I., Fraser, I. D. C. (2009). Suppression of LPS-Induced TNF-{alpha} Production in Macrophages by cAMP Is Mediated by PKA-AKAP95-p105. Sci Signal 2: ra28-ra28 [Abstract] [Full Text]  
  • Hashimoto, T., Yamauchi, L., Hunter, T., Kikkawa, U., Kamada, S. (2008). Possible involvement of caspase-7 in cell cycle progression at mitosis.. GENES CELLS 13: 609-621 [Abstract] [Full Text]  
  • Yang, Y., Mahaffey, C. L., Berube, N., Frankel, W. N. (2006). Interaction between Fidgetin and Protein Kinase A-anchoring Protein AKAP95 Is Critical for Palatogenesis in the Mouse. J. Biol. Chem. 281: 22352-22359 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»