This Article 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 Harada, S. Articles by Kieff, E. Search for Related Content PubMed PubMed Citation Articles by Harada, S. Articles by Kieff, E.

 Previous Article  |  Next Article 

J. Virol., 09 1997, 6611-6618, Vol 71, No. 9
Copyright © 1997, American Society for Microbiology

Epstein-Barr virus nuclear protein LP stimulates EBNA-2 acidic domain- mediated transcriptional activation

S Harada and E Kieff
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Epstein-Barr virus (EBV) nuclear proteins EBNA-LP and EBNA-2 are the first two proteins expressed in latent infection of primary B lymphocytes. EBNA-2 is essential for lymphocyte transformation, and EBNA-LP is at least critical. While EBNA-2 activates specific viral and cellular promoters, EBNA-LP's role has been obscure. We now show that EBNA-LP stimulates EBNA-2 activation of the LMP1 promoter and of the LMP1/LMP2B bidirectional transcriptional regulatory element. EBNA-LP alone has only a negative effect. EBNA-LP also stimulates EBNA-2 activation of a multimerized regulatory element from the BamC EBNA promoter. Since both viral regulatory elements can bind the EBNA-2- associated cell protein RBPJ kappa, consensus RBPJ kappa binding sites were positioned upstream of the herpes simplex virus type 1 thymidine kinase promoter and were found to be sufficient for EBNA-LP and EBNA-2 coactivation. EBNA-LP strongly stimulated activation of an adenovirus E1b promoter with upstream Gal4 binding sites by a Gal4 DNA binding domain/ EBNA-2 acidic domain fusion protein, indicating that EBNA-LP coactivation requires only the EBNA-2 acidic domain to be localized near a promoter. The EBNA-LP stimulatory activity resides in the amino- terminal 66-amino-acid repeat domain. The carboxyl-terminal unique 45 amino acids appear to regulate EBNA-LP's effects. The first 11 amino acids of the 45 have a strong negative effect, while the last 10 are critical for the ability of the last 34 to relieve the negative effect. These results indicate that EBNA-LP's critical role in EBV-mediated cell growth transformation is in stimulating (and probably regulating) EBNA-2-mediated transcriptional activation.

This article has been cited by other articles:

• Ling, P. D., Tan, J., Sewatanon, J., Peng, R. (2008). Murine Gammaherpesvirus 68 Open Reading Frame 75c Tegument Protein Induces the Degradation of PML and Is Essential for Production of Infectious Virus. J. Virol. 82: 8000-8012 [Abstract] [Full Text]  
• Garibal, J., Hollville, E., Bell, A. I., Kelly, G. L., Renouf, B., Kawaguchi, Y., Rickinson, A. B., Wiels, J. (2007). Truncated Form of the Epstein-Barr Virus Protein EBNA-LP Protects against Caspase-Dependent Apoptosis by Inhibiting Protein Phosphatase 2A. J. Virol. 81: 7598-7607 [Abstract] [Full Text]  
• Peng, C.-W., Zhao, B., Chen, H.-C., Chou, M.-L., Lai, C.-Y., Lin, S.-Z., Hsu, H.-Y., Kieff, E. (2007). Hsp72 up-regulates Epstein-Barr virus EBNALP coactivation with EBNA2. Blood 109: 5447-5454 [Abstract] [Full Text]  
• Portal, D., Rosendorff, A., Kieff, E. (2006). Epstein-Barr nuclear antigen leader protein coactivates transcription through interaction with histone deacetylase 4. Proc. Natl. Acad. Sci. USA 103: 19278-19283 [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]  
• Yue, W., Shackelford, J., Pagano, J. S. (2006). cdc2/Cyclin B1-Dependent Phosphorylation of EBNA2 at Ser243 Regulates Its Function in Mitosis. J. Virol. 80: 2045-2050 [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]  
• Yue, W., Gershburg, E., Pagano, J. S. (2005). Hyperphosphorylation of EBNA2 by Epstein-Barr Virus Protein Kinase Suppresses Transactivation of the LMP1 Promoter. J. Virol. 79: 5880-5885 [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]  
• Islas-Ohlmayer, M., Padgett-Thomas, A., Domiati-Saad, R., Melkus, M. W., Cravens, P. D., Martin, M. d. P., Netto, G., Garcia, J. V. (2004). Experimental Infection of NOD/SCID Mice Reconstituted with Human CD34+ Cells with Epstein-Barr Virus. J. Virol. 78: 13891-13900 [Abstract] [Full Text]  
• Lee, J. M., Lee, K.-H., Farrell, C. J., Ling, P. D., Kempkes, B., Park, J. H., Hayward, S. D. (2004). EBNA2 Is Required for Protection of Latently Epstein-Barr Virus-Infected B Cells against Specific Apoptotic Stimuli. J. Virol. 78: 12694-12697 [Abstract] [Full Text]  
• Peng, C.-W., Zhao, B., Kieff, E. (2004). Four EBNA2 Domains Are Important for EBNALP Coactivation. J. Virol. 78: 11439-11442 [Abstract] [Full Text]  
• Sutkowski, N., Chen, G., Calderon, G., Huber, B. T. (2004). Epstein-Barr Virus Latent Membrane Protein LMP-2A Is Sufficient for Transactivation of the Human Endogenous Retrovirus HERV-K18 Superantigen. J. Virol. 78: 7852-7860 [Abstract] [Full Text]  
• Smith, E., Sigvardsson, M. (2004). The roles of transcription factors in B lymphocyte commitment, development, and transformation. J. Leukoc. Biol. 75: 973-981 [Abstract] [Full Text]  
• Gordadze, A. V., Onunwor, C. W., Peng, R., Poston, D., Kremmer, E., Ling, P. D. (2004). EBNA2 Amino Acids 3 to 30 Are Required for Induction of LMP-1 and Immortalization Maintenance. J. Virol. 78: 3919-3929 [Abstract] [Full Text]  
• Kanamori, M., Watanabe, S., Honma, R., Kuroda, M., Imai, S., Takada, K., Yamamoto, N., Nishiyama, Y., Kawaguchi, Y. (2004). Epstein-Barr Virus Nuclear Antigen Leader Protein Induces Expression of Thymus- and Activation-Regulated Chemokine in B Cells. J. Virol. 78: 3984-3993 [Abstract] [Full Text]  
• Cahir-McFarland, E. D., Carter, K., Rosenwald, A., Giltnane, J. M., Henrickson, S. E., Staudt, L. M., Kieff, E. (2004). Role of NF-{kappa}B in Cell Survival and Transcription of Latent Membrane Protein 1-Expressing or Epstein-Barr Virus Latency III-Infected Cells. J. Virol. 78: 4108-4119 [Abstract] [Full Text]  
• Yue, W., Davenport, M. G., Shackelford, J., Pagano, J. S. (2004). Mitosis-Specific Hyperphosphorylation of Epstein-Barr Virus Nuclear Antigen 2 Suppresses Its Function. J. Virol. 78: 3542-3552 [Abstract] [Full Text]  
• Peng, C.-W., Xue, Y., Zhao, B., Johannsen, E., Kieff, E., Harada, S. (2004). Direct interactions between Epstein-Barr virus leader protein LP and the EBNA2 acidic domain underlie coordinate transcriptional regulation. Proc. Natl. Acad. Sci. USA 101: 1033-1038 [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]  
• Kato, K., Yokoyama, A., Tohya, Y., Akashi, H., Nishiyama, Y., Kawaguchi, Y. (2003). Identification of protein kinases responsible for phosphorylation of Epstein-Barr virus nuclear antigen leader protein at serine-35, which regulates its coactivator function. J. Gen. Virol. 84: 3381-3392 [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]  
• Ning, S., Hahn, A. M., Huye, L. E., Pagano, J. S. (2003). Interferon Regulatory Factor 7 Regulates Expression of Epstein-Barr Virus Latent Membrane Protein 1: a Regulatory Circuit. J. Virol. 77: 9359-9368 [Abstract] [Full Text]  
• Johansen, L. M., Deppmann, C. D., Erickson, K. D., Coffin, W. F. III, Thornton, T. M., Humphrey, S. E., Martin, J. M., Taparowsky, E. J. (2003). EBNA2 and Activated Notch Induce Expression of BATF. J. Virol. 77: 6029-6040 [Abstract] [Full Text]  
• Igarashi, M., Kawaguchi, Y., Hirai, K., Mizuno, F. (2003). Physical interaction of Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) with human oestrogen-related receptor 1 (hERR1): hERR1 interacts with a conserved domain of EBNA-LP that is critical for EBV-induced B-cell immortalization. J. Gen. Virol. 84: 319-327 [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]  
• Carter, K. L., Cahir-McFarland, E., Kieff, E. (2002). Epstein-Barr Virus-Induced Changes in B-Lymphocyte Gene Expression. J. Virol. 76: 10427-10436 [Abstract] [Full Text]  
• Dufva, M., Flodin, J., Nerstedt, A., Ruetschi, U., Rymo, L. (2002). Epstein-Barr virus nuclear antigen 5 inhibits pre-mRNA cleavage and polyadenylation. Nucleic Acids Res 30: 2131-2143 [Abstract] [Full Text]  
• Spender, L. C., Cornish, G. H., Sullivan, A., Farrell, P. J. (2002). Expression of Transcription Factor AML-2 (RUNX3, CBF{alpha}-3) Is Induced by Epstein-Barr Virus EBNA-2 and Correlates with the B-Cell Activation Phenotype. J. Virol. 76: 4919-4927 [Abstract] [Full Text]  
• Han, I., Xue, Y., Harada, S., Orstavik, S., Skalhegg, B., Kieff, E. (2002). Protein Kinase A Associates with HA95 and Affects Transcriptional Coactivation by Epstein-Barr Virus Nuclear Proteins. Mol. Cell. Biol. 22: 2136-2146 [Abstract] [Full Text]  
• Tanaka, M., Yokoyama, A., Igarashi, M., Matsuda, G., Kato, K., Kanamori, M., Hirai, K., Kawaguchi, Y., Yamanashi, Y. (2002). Conserved Region CR2 of Epstein-Barr Virus Nuclear Antigen Leader Protein Is a Multifunctional Domain That Mediates Self-Association as well as Nuclear Localization and Nuclear Matrix Association. J. Virol. 76: 1025-1032 [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]  
• McCann, E. M., Kelly, G. L., Rickinson, A. B., Bell, A. I. (2001). Genetic analysis of the Epstein-Barr virus-coded leader protein EBNA-LP as a co-activator of EBNA2 function. J. Gen. Virol. 82: 3067-3079 [Abstract] [Full Text]  
• Dufva, M., Olsson, M., Rymo, L. (2001). Epstein-Barr virus nuclear antigen 5 interacts with HAX-1, a possible component of the B-cell receptor signalling pathway. J. Gen. Virol. 82: 1581-1587 [Abstract] [Full Text]  
• Gordadze, A. V., Peng, R., Tan, J., Liu, G., Sutton, R., Kempkes, B., Bornkamm, G. W., Ling, P. D. (2001). Notch1IC Partially Replaces EBNA2 Function in B Cells Immortalized by Epstein-Barr Virus. J. Virol. 75: 5899-5912 [Abstract] [Full Text]  
• Yokoyama, A., Tanaka, M., Matsuda, G., Kato, K., Kanamori, M., Kawasaki, H., Hirano, H., Kitabayashi, I., Ohki, M., Hirai, K., Kawaguchi, Y. (2001). Identification of Major Phosphorylation Sites of Epstein-Barr Virus Nuclear Antigen Leader Protein (EBNA-LP): Ability of EBNA-LP To Induce Latent Membrane Protein 1 Cooperatively with EBNA-2 Is Regulated by Phosphorylation. J. Virol. 75: 5119-5128 [Abstract] [Full Text]  
• Höfelmayr, H., Strobl, L. J., Marschall, G., Bornkamm, G. W., Zimber-Strobl, U. (2001). Activated Notch1 Can Transiently Substitute for EBNA2 in the Maintenance of Proliferation of LMP1-Expressing Immortalized B Cells. J. Virol. 75: 2033-2040 [Abstract] [Full Text]  
• Han, I., Harada, S., Weaver, D., Xue, Y., Lane, W., Orstavik, S., Skalhegg, B., Kieff, E. (2001). EBNA-LP Associates with Cellular Proteins Including DNA-PK and HA95. J. Virol. 75: 2475-2481 [Abstract] [Full Text]  
• Harada, S., Yalamanchili, R., Kieff, E. (2001). Epstein-Barr Virus Nuclear Protein 2 Has at Least Two N-Terminal Domains That Mediate Self-Association. J. Virol. 75: 2482-2487 [Abstract] [Full Text]  
• Pokrovskaja, K., Mattsson, K., Kashuba, E., Klein, G., Szekely, L. (2001). Proteasome inhibitor induces nucleolar translocation of Epstein-Barr virus-encoded EBNA-5. J. Gen. Virol. 82: 345-358 [Abstract] [Full Text]  
• Peng, R., Tan, J., Ling, P. D. (2000). Conserved Regions in the Epstein-Barr Virus Leader Protein Define Distinct Domains Required for Nuclear Localization and Transcriptional Cooperation with EBNA2. J. Virol. 74: 9953-9963 [Abstract] [Full Text]  
• Kawaguchi, Y., Nakajima, K., Igarashi, M., Morita, T., Tanaka, M., Suzuki, M., Yokoyama, A., Matsuda, G., Kato, K., Kanamori, M., Hirai, K. (2000). Interaction of Epstein-Barr Virus Nuclear Antigen Leader Protein (EBNA-LP) with HS1-Associated Protein X-1: Implication of Cytoplasmic Function of EBNA-LP. J. Virol. 74: 10104-10111 [Abstract] [Full Text]  
• Young, L S, Dawson, C W, Eliopoulos, A G (2000). The expression and function of Epstein-Barr virus encoded latent genes. Mol. Pathol. 53: 238-247 [Abstract] [Full Text]  
• Webster-Cyriaque, J., Middeldorp, J., Raab-Traub, N. (2000). Hairy Leukoplakia: an Unusual Combination of Transforming and Permissive Epstein-Barr Virus Infections. J. Virol. 74: 7610-7618 [Abstract] [Full Text]  
• Zhao, B., Sample, C. E. (2000). 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. J. Virol. 74: 5151-5160 [Abstract] [Full Text]  
• Kirby, H., Rickinson, A., Bell, A. (2000). The activity of the Epstein-Barr virus BamHI W promoter in B cells is dependent on the binding of CREB/ATF factors. J. Gen. Virol. 81: 1057-1066 [Abstract] [Full Text]  
• Peng, R., Gordadze, A. V., Fuentes Pananá, E. M., Wang, F., Zong, J., Hayward, G. S., Tan, J., Ling, P. D. (2000). Sequence and Functional Analysis of EBNA-LP and EBNA2 Proteins from Nonhuman Primate Lymphocryptoviruses. J. Virol. 74: 379-389 [Abstract] [Full Text]  
• Gao, Y., Xue, S.-a., Griffin, B. E. (1999). Sensitivity of an Epstein-Barr Virus-Positive Tumor Line, Daudi, to Alpha Interferon Correlates with Expression of a GC-Rich Viral Transcript. Mol. Cell. Biol. 19: 7305-7313 [Abstract] [Full Text]  
• Sjöblom-Hallén, A., Yang, W., Jansson, A., Rymo, L. (1999). Silencing of the Epstein-Barr Virus Latent Membrane Protein 1 Gene by the Max-Mad1-mSin3A Modulator of Chromatin Structure. J. Virol. 73: 2983-2993 [Abstract] [Full Text]  
• Hsieh, J. J.-D., Zhou, S., Chen, L., Young, D. B., Hayward, S. D. (1999). CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex. Proc. Natl. Acad. Sci. USA 96: 23-28 [Abstract] [Full Text]  
• Harada, S., Yalamanchili, R., Kieff, E. (1998). Residues 231 to 280 of the Epstein-Barr Virus Nuclear Protein 2 Are Not Essential for Primary B-Lymphocyte Growth Transformation. J. Virol. 72: 9948-9954 [Abstract] [Full Text]  
• Kieff, E. (1998). Current Perspectives on the Molecular Pathogenesis of Virus-Induced Cancers in Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome. J Natl Cancer Inst Monogr 1998: 7-14 [Abstract] [Full Text]  
• Cludts, I., Farrell, P. J. (1998). Multiple Functions within the Epstein-Barr Virus EBNA-3A Protein. J. Virol. 72: 1862-1869 [Abstract] [Full Text]  
• Cahir-McFarland, E. D., Davidson, D. M., Schauer, S. L., Duong, J., Kieff, E. (2000). NF-kappa B inhibition causes spontaneous apoptosis in Epstein-Barr virus-transformed lymphoblastoid cells. Proc. Natl. Acad. Sci. USA 97: 6055-6060 [Abstract] [Full Text]