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 Knight, J. S.
Right arrow Articles by Robertson, E. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Knight, J. S.
Right arrow Articles by Robertson, E. S.

 Previous Article  |  Next Article 

Journal of Virology, February 2004, p. 1981-1991, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1981-1991.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus Nuclear Antigen 3C Regulates Cyclin A/p27 Complexes and Enhances Cyclin A-Dependent Kinase Activity

Jason S. Knight and Erle S. Robertson*

Department of Microbiology and Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104

Received 3 September 2003/ Accepted 29 October 2003

Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is essential for primary B-cell transformation. In this report we show that cyclin A, an activator of S phase progression, bound tightly to EBNA3C. EBNA3C interacted with cyclin A in vitro and associated with cyclin A complexes in EBV-transformed lymphoblastoid cell lines. Importantly, EBNA3C stimulated cyclin A-dependent kinase activity and rescued p27-mediated inhibition of cyclin A/Cdk2 kinase activity by decreasing the molecular association between cyclin A and p27 in cells. Additionally, phosphorylation of the retinoblastoma protein, a major regulator of cell cycle progression, was enhanced both in vitro and in vivo in the presence of EBNA3C. Cyclin A interacted with a region of the carboxy terminus of EBNA3C, shown to be important both for stimulation of cyclin A-dependent kinase activity and for cell cycle progression. This provides the first evidence of an essential EBV latent antigen's directly targeting a cell cycle regulatory protein and suggests a novel mechanism by which EBV deregulates the mammalian cell cycle, which is of critical importance in B-cell transformation.

* Corresponding author. Mailing address: Department of Microbiology and Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, 201 E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104. Phone: (215) 746-0114. Fax: (215) 898-9557. E-mail: erle{at}mail.med.upenn.edu.

Journal of Virology, February 2004, p. 1981-1991, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1981-1991.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Everly, D. N. Jr., Mainou, B. A., Raab-Traub, N. (2009). Transcriptional Downregulation of p27KIP1 through Regulation of E2F Function during LMP1-Mediated Transformation. J. Virol. 83: 12671-12679 [Abstract] [Full Text]  
  • Saha, A., Murakami, M., Kumar, P., Bajaj, B., Sims, K., Robertson, E. S. (2009). Epstein-Barr Virus Nuclear Antigen 3C Augments Mdm2-Mediated p53 Ubiquitination and Degradation by Deubiquitinating Mdm2. J. Virol. 83: 4652-4669 [Abstract] [Full Text]  
  • Maruo, S., Wu, Y., Ito, T., Kanda, T., Kieff, E. D., Takada, K. (2009). Epstein-Barr virus nuclear protein EBNA3C residues critical for maintaining lymphoblastoid cell growth. Proc. Natl. Acad. Sci. USA 106: 4419-4424 [Abstract] [Full Text]  
  • Bajaj, B. G., Murakami, M., Cai, Q., Verma, S. C., Lan, K., Robertson, E. S. (2008). Epstein-Barr Virus Nuclear Antigen 3C Interacts with and Enhances the Stability of the c-Myc Oncoprotein. J. Virol. 82: 4082-4090 [Abstract] [Full Text]  
  • Kashuba, E., Yurchenko, M., Yenamandra, S. P., Snopok, B., Isaguliants, M., Szekely, L., Klein, G. (2008). EBV-encoded EBNA-6 binds and targets MRS18-2 to the nucleus, resulting in the disruption of pRb-E2F1 complexes. Proc. Natl. Acad. Sci. USA 105: 5489-5494 [Abstract] [Full Text]  
  • 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]  
  • Munoz-Fontela, C., Garcia, M. A., Collado, M., Marcos-Villar, L., Gallego, P., Esteban, M., Rivas, C. (2007). Control of virus infection by tumour suppressors. Carcinogenesis 28: 1140-1144 [Abstract] [Full Text]  
  • Maruo, S., Wu, Y., Ishikawa, S., Kanda, T., Iwakiri, D., Takada, K. (2006). Epstein-Barr virus nuclear protein EBNA3C is required for cell cycle progression and growth maintenance of lymphoblastoid cells. Proc. Natl. Acad. Sci. USA 103: 19500-19505 [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]  
  • Knight, J. S., Sharma, N., Robertson, E. S. (2005). Epstein-Barr virus latent antigen 3C can mediate the degradation of the retinoblastoma protein through an SCF cellular ubiquitin ligase. Proc. Natl. Acad. Sci. USA 102: 18562-18566 [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]  
  • Everly, D. N. Jr., Mainou, B. A., Raab-Traub, N. (2004). Induction of Id1 and Id3 by Latent Membrane Protein 1 of Epstein-Barr Virus and Regulation of p27/Kip and Cyclin-Dependent Kinase 2 in Rodent Fibroblast Transformation. J. Virol. 78: 13470-13478 [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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»