This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Subramanian, C. Articles by Robertson, E. S. Search for Related Content PubMed PubMed Citation Articles by Subramanian, C. Articles by Robertson, E. S.

 Previous Article  |  Next Article 

Journal of Virology, May 2002, p. 4699-4708, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.4699-4708.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus Nuclear Antigen 3C and Prothymosin Alpha Interact with the p300 Transcriptional Coactivator at the CH1 and CH3/HAT Domains and Cooperate in Regulation of Transcription and Histone Acetylation

Department of Microbiology and Immunology and the Comprehensive Cancer and Geriatrics Center, University of Michigan Medical School, Ann Arbor, Michigan 48109-0934,¹ Institute of Veterinary Biochemistry, Universität Zürich-Irchel, 8057 Zürich, Switzerland,² Department of Medicine, University of Wales College of Medicine, Cardiff CF14 4XX, United Kingdom³

Received 23 January 2002/ Accepted 30 January 2002

The Epstein-Barr virus nuclear antigen 3C (EBNA3C), encoded by Epstein-Barr virus (EBV), is essential for mediating transformation of human B lymphocytes. Previous studies demonstrated that EBNA3C interacts with a small, nonhistone, highly acidic, high-mobility group-like nuclear protein prothymosin alpha (ProT) and the transcriptional coactivator p300 in complexes from EBV-infected cells. These complexes were shown to be associated with histone acetyltransferase (HAT) activity in that they were able to acetylate crude histones in vitro. In this report we show that ProT interacts with p300 similarly to p53 and other known oncoproteins at the CH1 amino-terminal domain as well as at a second domain downstream of the bromodomain which includes the CH3 region and HAT domain. Similarly, EBNA3C also interacts with p300 at regions which include the CH1 and CH3/HAT domains, suggesting that ProT and EBNAC3C may interact in a complex with p300. We also show that ProT activates transcription when targeted to promoters by fusion to the GAL4 DNA binding domain and that this activation is enhanced by the addition of an exogenous source of p300 under the control of a heterologous promoter. This overall activity is down-modulated in the presence of EBNA3C. These results further establish the interaction of cellular coactivator p300 with ProT and demonstrate that the associated activities resulting from this interaction, which plays a role in acetylation of histones and coactivation, can be regulated by EBNA3C. Furthermore, this study establishes for the first time a transcriptional role for ProT in recruitment or stabilization of coactivator p300, as well as other basal transcription factors, at the nucleosomes for regulation of transcription.

This article has been cited by other articles:

• Choudhuri, T., Verma, S. C., Lan, K., Murakami, M., Robertson, E. S. (2007). The ATM/ATR Signaling Effector Chk2 Is Targeted by Epstein-Barr Virus Nuclear Antigen 3C To Release the G2/M Cell Cycle Block. J. Virol. 81: 6718-6730 [Abstract] [Full Text]  
• Jimenez-Ramirez, C., Brooks, A. J., Forshell, L. P., Yakimchuk, K., Zhao, B., Fulgham, T. Z., Sample, C. E. (2006). Epstein-Barr Virus EBNA-3C Is Targeted to and Regulates Expression from the Bidirectional LMP-1/2B Promoter. J. Virol. 80: 11200-11208 [Abstract] [Full Text]  
• Covelo, G., Sarandeses, C. S., Diaz-Jullien, C., Freire, M. (2006). Prothymosin {alpha} Interacts with Free Core Histones in the Nucleus of Dividing Cells. J Biochem 140: 627-637 [Abstract] [Full Text]  
• Mosoian, A., Teixeira, A., High, A. A., Christian, R. E., Hunt, D. F., Shabanowitz, J., Liu, X., Klotman, M. (2006). Novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages.. J. Virol. 80: 9200-9206 [Abstract] [Full Text]  
• Kobayashi, T., Wang, T., Maezawa, M., Kobayashi, M., Ohnishi, S., Hatanaka, K., Hige, S., Shimizu, Y., Kato, M., Asaka, M., Tanaka, J., Imamura, M., Hasegawa, K., Tanaka, Y., Brachmann, R. K. (2006). Overexpression of the Oncoprotein Prothymosin {alpha} Triggers a p53 Response that Involves p53 Acetylation.. Cancer Res. 66: 3137-3144 [Abstract] [Full Text]  
• Okamoto, K., Isohashi, F. (2005). Macromolecular Translocation Inhibitor II (Zn2+-binding Protein, Parathymosin) Interacts with the Glucocorticoid Receptor and Enhances Transcription in Vivo. J. Biol. Chem. 280: 36986-36993 [Abstract] [Full Text]  
• Kuppers, D. A., Lan, K., Knight, J. S., Robertson, E. S. (2005). Regulation of Matrix Metalloproteinase 9 Expression by Epstein-Barr Virus Nuclear Antigen 3C and the Suppressor of Metastasis Nm23-H1. J. Virol. 79: 9714-9724 [Abstract] [Full Text]  
• Touitou, R., O'Nions, J., Heaney, J., Allday, M. J. (2005). Epstein-Barr virus EBNA3 proteins bind to the C8/{alpha}7 subunit of the 20S proteasome and are degraded by 20S proteasomes in vitro, but are very stable in latently infected B cells. J. Gen. Virol. 86: 1269-1277 [Abstract] [Full Text]  
• Knight, J. S., Sharma, N., Robertson, E. S. (2005). SCFSkp2 Complex Targeted by Epstein-Barr Virus Essential Nuclear Antigen. Mol. Cell. Biol. 25: 1749-1763 [Abstract] [Full Text]  
• Knight, J. S., Sharma, N., Kalman, D. E., Robertson, E. S. (2004). A Cyclin-Binding Motif within the Amino-Terminal Homology Domain of EBNA3C Binds Cyclin A and Modulates Cyclin A-Dependent Kinase Activity in Epstein-Barr Virus-Infected Cells. J. Virol. 78: 12857-12867 [Abstract] [Full Text]  
• Kent, J. R., Zeng, P.-Y., Atanasiu, D., Gardner, J., Fraser, N. W., Berger, S. L. (2004). During Lytic Infection Herpes Simplex Virus Type 1 Is Associated with Histones Bearing Modifications That Correlate with Active Transcription. J. Virol. 78: 10178-10186 [Abstract] [Full Text]  
• West, M. J., Webb, H. M., Sinclair, A. J., Woolfson, D. N. (2004). Biophysical and Mutational Analysis of the Putative bZIP Domain of Epstein-Barr Virus EBNA 3C. J. Virol. 78: 9431-9445 [Abstract] [Full Text]  
• Eeckhoute, J., Formstecher, P., Laine, B. (2004). Hepatocyte Nuclear Factor 4{alpha} enhances the Hepatocyte Nuclear Factor 1{alpha}-mediated activation of transcription. Nucleic Acids Res 32: 2586-2593 [Abstract] [Full Text]  
• Knight, J. S., Robertson, E. S. (2004). Epstein-Barr Virus Nuclear Antigen 3C Regulates Cyclin A/p27 Complexes and Enhances Cyclin A-Dependent Kinase Activity. J. Virol. 78: 1981-1991 [Abstract] [Full Text]  
• Rosendorff, A., Illanes, D., David, G., Lin, J., Kieff, E., Johannsen, E. (2004). EBNA3C Coactivation with EBNA2 Requires a SUMO Homology Domain. J. Virol. 78: 367-377 [Abstract] [Full Text]  
• Subramanian, C., Robertson, E. S. (2002). The Metastatic Suppressor Nm23-H1 Interacts with EBNA3C at Sequences Located between the Glutamine- and Proline-Rich Domains and Can Cooperate in Activation of Transcription. J. Virol. 76: 8702-8709 [Abstract] [Full Text]