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 Zhao, L. Y.
Right arrow Articles by Liao, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, L. Y.
Right arrow Articles by Liao, D.

 Previous Article  |  Next Article 

Journal of Virology, December 2003, p. 13171-13181, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13171-13181.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Sequestration of p53 in the Cytoplasm by Adenovirus Type 12 E1B 55-Kilodalton Oncoprotein Is Required for Inhibition of p53-Mediated Apoptosis

Lisa Y. Zhao and Daiqing Liao*

Department of Anatomy and Cell Biology and UF Shands Cancer Center, University of Florida College of Medicine, Gainesville, Florida 32610-0235

Received 15 July 2003/ Accepted 4 September 2003

The adenovirus E1B 55-kDa protein is a potent inhibitor of p53-mediated transactivation and apoptosis. The proposed mechanisms include tethering the E1B repression domain to p53-responsive promoters via direct E1B-p53 interaction. Cytoplasmic sequestration of p53 by the 55-kDa protein would impose additional inhibition on p53-mediated effects. To investigate further the role of cytoplasmic sequestration of p53 in its inhibition by the E1B 55-kDa protein we systematically examined domains in both the Ad12 55-kDa protein and p53 that underpin their colocalization in the cytoplasmic body and show that the N-terminal transactivation domain (TAD) of p53 is essential for retaining p53 in the cytoplasmic body. Deletion of amino acids 11 to 27 or even point mutation L22Q/W23S abolished the localization of p53 to the cytoplasmic body, whereas other parts of TAD and the C-terminal domain of p53 are dispensable. This cytoplasmic body is distinct from aggresome associated with overexpression of some proteins, since it neither altered vimentin intermediate filaments nor associated with centrosome or ubiquitin. Formation of this structure is sensitive to mutation of the Ad12 55-kDa protein. Strikingly, mutation S476/477A near the C terminus of the Ad12 55-kDa protein eliminated the formation of the cytoplasmic body. The equivalent residues in the Ad5 55-kDa protein were shown to be critical for its ability to inhibit p53. Indeed, Ad12 55-kDa mutants that cannot form a cytoplasmic body can no longer inhibit p53-mediated effects. Conversely, the Ad12 55-kDa protein does not suppress p53 mutant L22Q/W23S-mediated apoptosis. Finally, we show that E1B can still sequester p53 that contains the mitochondrial import sequence, thereby potentially preventing the localization of p53 to mitochondria. Thus, cytoplasmic sequestration of p53 by the E1B 55-kDa protein plays an important role in restricting p53 activities.

* Corresponding author. Mailing address: Department of Anatomy and Cell Biology, University of Florida College of Medicine, P.O. Box 100235, 1600 SW Archer Rd., Gainesville, FL 32610-0235. Phone: (352) 294-7976. Fax: (352) 392-3305. E-mail: dliao{at}ufl.edu.

Journal of Virology, December 2003, p. 13171-13181, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13171-13181.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Miron, M.-J., Blanchette, P., Groitl, P., Dallaire, F., Teodoro, J. G., Li, S., Dobner, T., Branton, P. E. (2009). Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection. J. Virol. 83: 1689-1699 [Abstract] [Full Text]  
  • Schwartz, R. A., Lakdawala, S. S., Eshleman, H. D., Russell, M. R., Carson, C. T., Weitzman, M. D. (2008). Distinct Requirements of Adenovirus E1b55K Protein for Degradation of Cellular Substrates. J. Virol. 82: 9043-9055 [Abstract] [Full Text]  
  • Bottger, S., Jerszyk, E., Low, B., Walker, C. (2008). Genotoxic Stress-Induced Expression of p53 and Apoptosis in Leukemic Clam Hemocytes with Cytoplasmically Sequestered p53. Cancer Res. 68: 777-782 [Abstract] [Full Text]  
  • Zhao, L. Y., Santiago, A., Liu, J., Liao, D. (2007). Repression of p53-mediated Transcription by Adenovirus E1B 55-kDa Does Not Require Corepressor mSin3A and Histone Deacetylases. J. Biol. Chem. 282: 7001-7010 [Abstract] [Full Text]  
  • Deng, X., Gao, F., Flagg, T., Anderson, J., May, W. S. (2006). Bcl2's Flexible Loop Domain Regulates p53 Binding and Survival. Mol. Cell. Biol. 26: 4421-4434 [Abstract] [Full Text]  
  • Utama, B., Shen, Y. H., Mitchell, B. M., Makagiansar, I. T., Gan, Y., Muthuswamy, R., Duraisamy, S., Martin, D., Wang, X., Zhang, M.-X., Wang, J., Wang, J., Vercellotti, G. M., Gu, W., Li Wang, X. (2006). Mechanisms for human cytomegalovirus-induced cytoplasmic p53 sequestration in endothelial cells. J. Cell Sci. 119: 2457-2467 [Abstract] [Full Text]  
  • Dove, B., Brooks, G., Bicknell, K., Wurm, T., Hiscox, J. A. (2006). Cell cycle perturbations induced by infection with the coronavirus infectious bronchitis virus and their effect on virus replication.. J. Virol. 80: 4147-4156 [Abstract] [Full Text]  
  • Kaul, S. C., Aida, S., Yaguchi, T., Kaur, K., Wadhwa, R. (2005). Activation of Wild Type p53 Function by Its Mortalin-binding, Cytoplasmically Localizing Carboxyl Terminus Peptides. J. Biol. Chem. 280: 39373-39379 [Abstract] [Full Text]  
  • Golubovskaya, V. M., Finch, R., Cance, W. G. (2005). Direct Interaction of the N-terminal Domain of Focal Adhesion Kinase with the N-terminal Transactivation Domain of p53. J. Biol. Chem. 280: 25008-25021 [Abstract] [Full Text]  
  • Zhao, L. Y., Liu, J., Sidhu, G. S., Niu, Y., Liu, Y., Wang, R., Liao, D. (2004). Negative Regulation of p53 Functions by Daxx and the Involvement of MDM2. J. Biol. Chem. 279: 50566-50579 [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»