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, B.
Right arrow Articles by Sample, C. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, B.
Right arrow Articles by Sample, C. E.

 Previous Article  |  Next Article 

Journal of Virology, June 2000, p. 5151-5160, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Epstein-Barr Virus Nuclear Antigen 3C Activates the Latent Membrane Protein 1 Promoter in the Presence of Epstein-Barr Virus Nuclear Antigen 2 through Sequences Encompassing an Spi-1/Spi-B Binding Site

Bo Zhaodagger and Clare E. Sample*

Program in Viral Oncogenesis and Tumor Immunology, Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, and Department of Pathology, University of Tennessee College of Medicine, Memphis, Tennessee 38163

Received 9 February 2000/Accepted 16 March 2000

The Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) protein is a transcriptional regulator of viral and cellular genes that is essential for EBV-mediated immortalization of B lymphocytes in vitro. EBNA-3C can inhibit transcription through an association with the cellular DNA-binding protein Jkappa , a function shared by EBNA-3A and EBNA-3B. Here, we report a mechanism by which EBNA-3C can activate transcription from the EBV latent membrane protein 1 (LMP-1) promoter in conjunction with EBNA-2. Jkappa DNA-binding sites were not required for this activation, and a mutant EBNA-3C protein unable to bind Jkappa activated transcription as efficiently as wild-type EBNA-3C, indicating that EBNA-3C can regulate transcription through a mechanism that is independent of Jkappa . Furthermore, activation of the LMP-1 promoter is a unique function of EBNA-3C, not shared by EBNA-3A and EBNA-3B. The DNA element through which EBNA-3C activates the LMP-1 promoter includes a Spi-1/Spi-B binding site, previously characterized as an important EBNA-2 response element. Although this element has considerable homology to mouse immunoglobulin light chain promoter sequences to which the mouse homologue of Spi-1 binds with its dimerization partner IRF4, we demonstrate that the IRF4-like binding sites in the LMP-1 promoter do not play a role in EBNA-3C-mediated activation. Both EBNA-2 and EBNA-3C were required for transcription mediated through a 41-bp region of the LMP-1 promoter encompassing the Spi binding site. However, EBNA-3C had no effect on transcription mediated in conjunction with the EBNA-2 activation domain fused to the GAL4 DNA-binding domain, suggesting that it does not function as an adapter between EBNA-2 and the cellular transcriptional machinery. Like EBNA-2, EBNA-3C bound directly to both Spi-1 and Spi-B in vitro. This interaction was mediated by a region of EBNA-3C encompassing a likely basic leucine zipper (bZIP) domain and the ets domain of Spi-1 or Spi-B, reminiscent of interactions between bZIP and ets domains of other transcription factors that result in their targeting to DNA. There are many examples of regulation of the hematopoietic-specific Spi transcription factors through protein-protein interactions, and a similar regulation by EBNA-3C, in conjunction with EBNA-2, is likely to be an important and unique contribution of EBNA-3C to EBV-mediated immortalization.

* Corresponding author. Mailing address: Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105. Phone: (901) 495-3416. Fax: (901) 523-2622. E-mail: clare.sample{at}stjude.org.

dagger Present address: Departments of Microbiology and Molecular Genetics, Channing Laboratory, Harvard Medical School, Boston, MA 02115.

Journal of Virology, June 2000, p. 5151-5160, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lee, S., Sakakibara, S., Maruo, S., Zhao, B., Calderwood, M. A., Holthaus, A. M., Lai, C.-Y., Takada, K., Kieff, E., Johannsen, E. (2009). Epstein-Barr Virus Nuclear Protein 3C Domains Necessary for Lymphoblastoid Cell Growth: Interaction with RBP-J{kappa} Regulates TCL1. J. Virol. 83: 12368-12377 [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]  
  • Cameron, J. E., Yin, Q., Fewell, C., Lacey, M., McBride, J., Wang, X., Lin, Z., Schaefer, B. C., Flemington, E. K. (2008). Epstein-Barr Virus Latent Membrane Protein 1 Induces Cellular MicroRNA miR-146a, a Modulator of Lymphocyte Signaling Pathways. J. Virol. 82: 1946-1958 [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]  
  • 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]  
  • Chen, A., Zhao, B., Kieff, E., Aster, J. C., Wang, F. (2006). EBNA-3B- and EBNA-3C-Regulated Cellular Genes in Epstein-Barr Virus-Immortalized Lymphoblastoid Cell Lines.. J. Virol. 80: 10139-10150 [Abstract] [Full Text]  
  • Goormachtigh, G., Ouk, T.-S., Mougel, A., Tranchand-Bunel, D., Masy, E., Le Clorennec, C., Feuillard, J., Bornkamm, G. W., Auriault, C., Manet, E., Fafeur, V., Adriaenssens, E., Coll, J. (2006). Autoactivation of the Epstein-Barr Virus Oncogenic Protein LMP1 during Type II Latency through Opposite Roles of the NF-{kappa}B and JNK Signaling Pathways.. J. Virol. 80: 7382-7393 [Abstract] [Full Text]  
  • Pegman, P. M., Smith, S. M., D'Souza, B. N., Loughran, S. T., Maier, S., Kempkes, B., Cahill, P. A., Simmons, M. J., Gelinas, C., Walls, D. (2006). Epstein-Barr Virus Nuclear Antigen 2 trans-Activates the Cellular Antiapoptotic bfl-1 Gene by a CBF1/RBPJ{kappa}-Dependent Pathway.. J. Virol. 80: 8133-8144 [Abstract] [Full Text]  
  • Maruo, S., Johannsen, E., Illanes, D., Cooper, A., Zhao, B., Kieff, E. (2005). Epstein-Barr Virus Nuclear Protein 3A Domains Essential for Growth of Lymphoblasts: Transcriptional Regulation through RBP-J{kappa}/CBF1 Is Critical. J. Virol. 79: 10171-10179 [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]  
  • Peng, R., Moses, S. C., Tan, J., Kremmer, E., Ling, P. D. (2005). The Epstein-Barr Virus EBNA-LP Protein Preferentially Coactivates EBNA2-Mediated Stimulation of Latent Membrane Proteins Expressed from the Viral Divergent Promoter. J. Virol. 79: 4492-4505 [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]  
  • Chang, Y., Lee, H.-H., Chang, S.-S., Hsu, T.-Y., Wang, P.-W., Chang, Y.-S., Takada, K., Tsai, C.-H. (2004). Induction of Epstein-Barr Virus Latent Membrane Protein 1 by a Lytic Transactivator Rta. J. Virol. 78: 13028-13036 [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]  
  • 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]  
  • Maruo, S., Johannsen, E., Illanes, D., Cooper, A., Kieff, E. (2003). Epstein-Barr Virus Nuclear Protein EBNA3A Is Critical for Maintaining Lymphoblastoid Cell Line Growth. J. Virol. 77: 10437-10447 [Abstract] [Full Text]  
  • Zhao, B., Dalbies-Tran, R., Jiang, H., Ruf, I. K., Sample, J. T., Wang, F., Sample, C. E. (2003). Transcriptional Regulatory Properties of Epstein-Barr Virus Nuclear Antigen 3C Are Conserved in Simian Lymphocryptoviruses. J. Virol. 77: 5639-5648 [Abstract] [Full Text]  
  • Chen, H., Hutt-Fletcher, L., Cao, L., Hayward, S. D. (2003). A Positive Autoregulatory Loop of LMP1 Expression and STAT Activation in Epithelial Cells Latently Infected with Epstein-Barr Virus. J. Virol. 77: 4139-4148 [Abstract] [Full Text]  
  • Knight, J. S., Lan, K., Subramanian, C., Robertson, E. S. (2003). Epstein-Barr Virus Nuclear Antigen 3C Recruits Histone Deacetylase Activity and Associates with the Corepressors mSin3A and NCoR in Human B-Cell Lines. J. Virol. 77: 4261-4272 [Abstract] [Full Text]  
  • Cooper, A., Johannsen, E., Maruo, S., Cahir-McFarland, E., Illanes, D., Davidson, D., Kieff, E. (2002). EBNA3A Association with RBP-J{kappa} Down-Regulates c-myc and Epstein-Barr Virus-Transformed Lymphoblast Growth. J. Virol. 77: 999-1010 [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]  
  • Gordadze, A. V., Poston, D., Ling, P. D. (2002). The EBNA2 Polyproline Region Is Dispensable for Epstein-Barr Virus-Mediated Immortalization Maintenance. J. Virol. 76: 7349-7355 [Abstract] [Full Text]  
  • Hille, A., Badu-Antwi, A., Holzer, D., Grasser, F. A. (2002). Lysine residues of Epstein-Barr virus-encoded nuclear antigen 2 do not confer secondary modifications via ubiquitin or SUMO-like proteins but modulate transcriptional activation. J. Gen. Virol. 83: 1037-1042 [Abstract] [Full Text]  
  • Subramanian, C., Hasan, S., Rowe, M., Hottiger, M., Orre, R., Robertson, E. S. (2002). 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. J. Virol. 76: 4699-4708 [Abstract] [Full Text]  
  • Lin, J., Johannsen, E., Robertson, E., Kieff, E. (2002). Epstein-Barr Virus Nuclear Antigen 3C Putative Repression Domain Mediates Coactivation of the LMP1 Promoter with EBNA-2. J. Virol. 76: 232-242 [Abstract] [Full Text]  
  • Groves, A. K., Cotter, M. A., Subramanian, C., Robertson, E. S. (2001). The Latency-Associated Nuclear Antigen Encoded by Kaposi's Sarcoma-Associated Herpesvirus Activates Two Major Essential Epstein-Barr Virus Latent Promoters. J. Virol. 75: 9446-9457 [Abstract] [Full Text]  
  • Touitou, R., Hickabottom, M., Parker, G., Crook, T., Allday, M. J. (2001). Physical and Functional Interactions between the Corepressor CtBP and the Epstein-Barr Virus Nuclear Antigen EBNA3C. J. Virol. 75: 7749-7755 [Abstract] [Full Text]  
  • Salamon, D., Takacs, M., Ujvari, D., Uhlig, J., Wolf, H., Minarovits, J., Niller, H. H. (2001). Protein-DNA Binding and CpG Methylation at Nucleotide Resolution of Latency-Associated Promoters Qp, Cp, and LMP1p of Epstein-Barr Virus. J. Virol. 75: 2584-2596 [Abstract] [Full Text]  
  • Dalbiès-Tran, R., Stigger-Rosser, E., Dotson, T., Sample, C. E. (2001). Amino Acids of Epstein-Barr Virus Nuclear Antigen 3A Essential for Repression of J{kappa}-Mediated Transcription and Their Evolutionary Conservation. J. Virol. 75: 90-99 [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»