Previous Article | Next Article 
Journal of Virology, August 2004, p. 8245-8253, Vol. 78, No. 15
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.15.8245-8253.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
p53 Targets Simian Virus 40 Large T Antigen for Acetylation by CBP
Danielle L. Poulin, Andrew L. Kung, and James A. DeCaprio*
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115
Received 10 February 2004/
Accepted 18 March 2004
Simian virus 40 (SV40) large T antigen (T Ag) interacts with the tumor suppressor p53 and the transcriptional coactivators CBP and p300. Binding of these cellular proteins in a ternary complex has been implicated in T Ag-mediated transformation. It has been suggested that the ability of CBP/p300 to modulate p53 function underlies p53's regulation of cell proliferation and tumorigenesis. In this study, we provide further evidence that CBP activity may be mediated through its synergistic action with p53. We demonstrate that SV40 T Ag is acetylated in vivo in a p53-dependent manner and T Ag acetylation is largely mediated by CBP. The acetylation of T Ag is dependent on its interaction with p53 and on p53's interaction with CBP. We have mapped the site of acetylation on T Ag to the C-terminal lysine residue 697. This acetylation site is conserved between the T antigens of the human polyomaviruses JC and BK, which are also known to interact with p53. We show that both JC and BK T antigens are also acetylated at corresponding sites in vivo. While other proteins are known to be acetylated by CBP/p300, none are known to depend on p53 for acetylation. T Ag acetylation may provide a regulatory mechanism for T Ag binding to a cellular factor or play a role in another aspect of T Ag function.
* Corresponding author. Mailing address: Dana-Farber Cancer Institute, Mayer 457, 44 Binney St., Boston, MA 02115. Phone: (617) 632-3825. Fax: (617) 632-4760. E-mail:
james_decaprio{at}dfci.harvard.edu.
Journal of Virology, August 2004, p. 8245-8253, Vol. 78, No. 15
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.15.8245-8253.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Hermannstadter, A., Ziegler, C., Kuhl, M., Deppert, W., Tolstonog, G. V.
(2009). Wild-Type p53 Enhances Efficiency of Simian Virus 40 Large-T-Antigen-Induced Cellular Transformation. J. Virol.
83: 10106-10118
[Abstract]
[Full Text]
-
Rathi, A. V., Saenz Robles, M. T., Cantalupo, P. G., Whitehead, R. H., Pipas, J. M.
(2009). Simian Virus 40 T-Antigen-Mediated Gene Regulation in Enterocytes Is Controlled Primarily by the Rb-E2F Pathway. J. Virol.
83: 9521-9531
[Abstract]
[Full Text]
-
Ahuja, D., Rathi, A. V., Greer, A. E., Chen, X. S., Pipas, J. M.
(2009). A Structure-Guided Mutational Analysis of Simian Virus 40 Large T Antigen: Identification of Surface Residues Required for Viral Replication and Transformation. J. Virol.
83: 8781-8788
[Abstract]
[Full Text]
-
Miller, C. L., Arnold, M. M., Broering, T. J., Eichwald, C., Kim, J., Dinoso, J. B., Nibert, M. L.
(2007). Virus-derived Platforms for Visualizing Protein Associations inside Cells. Mol. Cell. Proteomics
6: 1027-1038
[Abstract]
[Full Text]
-
Shimazu, T., Horinouchi, S., Yoshida, M.
(2007). Multiple Histone Deacetylases and the CREB-binding Protein Regulate Pre-mRNA 3'-End Processing. J. Biol. Chem.
282: 4470-4478
[Abstract]
[Full Text]
-
Borger, D. R., DeCaprio, J. A.
(2006). Targeting of p300/CREB Binding Protein Coactivators by Simian Virus 40 Is Mediated through p53. J. Virol.
80: 4292-4303
[Abstract]
[Full Text]
-
Kasper, J. S., Kuwabara, H., Arai, T., Ali, S. H., DeCaprio, J. A.
(2005). Simian Virus 40 Large T Antigen's Association with the CUL7 SCF Complex Contributes to Cellular Transformation. J. Virol.
79: 11685-11692
[Abstract]
[Full Text]