Transcriptional repression by the Epstein-Barr virus EBNA3A protein tethered to DNA does not require RBP-Jkappa Free

Abstract

The Epstein-Barr virus (EBV) proteins EBNA1, EBNA2, EBNA3A, EBNA3C, LMP1 and EBNA-LP are essential for the immortalization of primary B lymphocytes by EBV. EBNA2 is a transcriptional activator of viral and cellular genes. Both EBNA3A and EBNA3C have been shown to specifically inhibit EBNA2-activated transcription by direct interaction with RBP-J, a cellular DNA-binding factor known to recruit EBNA2 to EBNA2-responsive genes. This interaction interferes with the binding of RBP-J to DNA , and this is probably the mechanism by which EBNA3A and EBNA3C repress EBNA2-acti- vated transcription . EBNA3A and EBNA3C also directly repress transcription when tethered to a promoter via the DNA-binding domain of the yeast Gal4 protein. As RBP-J has been previously shown to be a repressor in mammalian cells, this repression could be due to the recruitment of RBP-J by Gal4-EBNA3A and 3C. In this study, we have precisely mapped the domain of EBNA3A involved in the interaction with RBP-J and we have shown that interaction with RBP-J is not required for the Gal4-EBNA3A-mediated repression. Furthermore, we have characterized in EBNA3A a domain of 143 amino acids which is necessary and sufficient for EBNA3A-dependent repression.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-79-2-363
1998-02-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/79/2/9472621.html?itemId=/content/journal/jgv/10.1099/0022-1317-79-2-363&mimeType=html&fmt=ahah

References

  1. Abbot S. D., Rowe M., Cadwallader K., Ricksten A., Gordon J., Wang F., Rymo L., Rickinson A. B. 1990; Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein. Journal of Virology 64:2126–2134
    [Google Scholar]
  2. Allday M. J., Farrell P. J. 1994; Epstein-Barr virus nuclear antigen EBNA3C/6 expression maintains the level of latent membrane protein 1 in G1-arrested cells. Journal of Virology 68:3491–3498
    [Google Scholar]
  3. Bain M., Watson R. J., Farrell P. J., Allday M. J. 1996; Epstein-Barr virus nuclear antigen 3C is a powerful repressor of transcription when tethered to DNA. Journal of Virology 70:2481–2489
    [Google Scholar]
  4. Calender A., Billaud M., Aubry J.-P., Banchereau J., Vuillaume M., Lenoir G. M. 1987; Epstein -Barr virus (EBV) induces expression of B- cell activation markers on in vitro infection of EBV-negative B-lymphoma cells. Proceedings of the National Academy of Sciences, USA 84:8060–8064
    [Google Scholar]
  5. Cohen J. F., Wang F., Mannick J., Kieff E. 1989; Epstein -Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. Proceedings of the National Academy of Sciences, USA 86:9558–9562
    [Google Scholar]
  6. Cordier M., Calender A., Billaud M., Zimber U., Rousselet G., Pavlish O., Banchereau J., Tursz T., Bornkamm G., Lenoir G. M. 1990; Stable transfection of Epstein-Barr virus (EBV) nuclear antigen 2 in lymphoma cells containing the EBVP3HR1 genome induces expression of B-cell activation molecules CD21 and CD23. Journal of Virology 64:1002–1013
    [Google Scholar]
  7. Dou S., Zeng X., Cortes P., Erdjument-Bromage H., Temps P., Honjo T., Vales L. D. 1994; The recombination signal sequence-binding protein RBP-2N functions as a transcriptional repressor. Molecular and Cellular Biology 14:3310–3319
    [Google Scholar]
  8. Fahraeus R., Jansson A., Ricksten A., Sjöblom A., Rymo L. 1990; Epstein-Barr virus-encoded nuclear antigen 2 activates the viral latent membrane protein promoter by modulating the activity of a negative regulatory element. Proceedings of the National Academy of Sciences, USA 87:7390–7394
    [Google Scholar]
  9. Grossman S. R., Johannsen E., Tong X., Yalamanchili R., Kieff E. 1994; The Epstein-Barr virus nuclear antigen 2 transactivator is directed to response elements by the J k recombination signal binding protein. Proceedings of the National Academy of Sciences, USA 91:7568–7572
    [Google Scholar]
  10. Hammerschmidt W., Sugden B. 1989; Genetic analysis of immortalizing functions of Epstein-Barr virus in human B lymphocytes. Nature 340:393–397
    [Google Scholar]
  11. Hammerschmidt W. B., Sugden B., Baichwal V. 1989; The transforming domain alone of latent membrane protein of Epstein-Barr virus is toxic when expressed at high levels. Journal of Virology 63:2469–24 75
    [Google Scholar]
  12. Henkel T., Ling P. D., Hayward L. S. D., Peterson M. G. 1994; Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J k . Science 265:92–95
    [Google Scholar]
  13. Hsieh J.J.-D., Hayward S. D. 1995; Masking of the CBF1/RBPJK transcriptional repression domain by Epstein-Barr virus EBNA2. Science 238:560–563
    [Google Scholar]
  14. Kallin B., Dillner J., Ernberg I., Ehlin-Henriksson B., Rosen A., Henle W., Klein G. 1986; Four virally determined nuclear antigens are expressed in Epstein-Barr virus-transformed cells. Proceedings of the National Academy of Sciences, USA 83:1499–1503
    [Google Scholar]
  15. Kaye K. M., Izumi K. M., Kieff E. 1993; Epstein-Barr virus latent membrane protein 1 is essential for B lymphocytes growth trans-formation. Proceedings of the National Academy of Sciences, USA 68:9150–9154
    [Google Scholar]
  16. Kempkes B., Spitkovsky D., Jansen-Dürr P., Ellwart J. W., Kremmer E., Delecluse H.-J., Rottenberger C., Bornkamm G. W., Hammerschmidt W. 1995; B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2. EMBO Journal 14:88–96
    [Google Scholar]
  17. Kieff E. D. 1996; Epstein-Barr virus. In Fields Virology, 3rd edn. pp 2343–2396 Fields B. N., Knipe D. M., Howley P. M. Edited by Philadelphia: Lippincott-Raven;
    [Google Scholar]
  18. Kienzle N., Young D., Silins S., Sculley T. B. 1996; Induction of pleckstrin by the Epstein-Barr virus nuclear antigen 3 family. Virology 224:167–174
    [Google Scholar]
  19. Knuston J. C. 1990; The level of c-fgr RNA is increased by EBNA-2, an Epstein-Barr virus gene required for cell immortalization. Journal of Virology 64:2530–2536
    [Google Scholar]
  20. Krauer K. G., Kienzle N., Young D. B., Sculley T. B. 1996; Epstein-Barr nuclear antigen-3 and-4 interact with RBP2N a major isoform of RBP-J k in B lymphocytes. Virology 226:346–353
    [Google Scholar]
  21. Le Roux A., Kerdiles B., Walls D., Dedieu J. F., Perricaudet M. 1994; The Epstein-Barr virus determined nuclear antigens EBNA-3A, 3B, 3C repress EBNA-2-mediated transactivation of the viral terminal protein 1 gene promoter. Virology 205:596–602
    [Google Scholar]
  22. Ling P. D., Rawlins D. R., Hayward S. D. 1993; The Epstein-Barr virus immortalizing protein EBNA-2 is targeted to DNA by a cellular enhancer-binding protein. Proceedings of the National Academy of Sciences, USA 90:9237–9241
    [Google Scholar]
  23. Mannick J. B., Cohen J. L., Birkenbach M., Marchini A., Kieff E. 1991; The Epstein-Barr virus nuclear protein encoded by the leader of the EBNA RNAs (EBNA-LP) is important in B-lymphocyte transformation. Journal of Virology 65:6826–6837
    [Google Scholar]
  24. Marshall D., Sample C. 1995; Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator. Journal of Virology 69:3624–3630
    [Google Scholar]
  25. Martin J. M., Veis D., Korsmeyer S. J., Sugden B. 1993; Latent membrane protein of Epstein-Barr virus induces cellular phenotypes independently of expression of Bcl-2. Journal of Virology 67:5269–5278
    [Google Scholar]
  26. Parker G. A., Crook T., Bain M., Sara E. A., Farrell P. J., Allday M. J. 1996; Epstein-Barr virus nuclear antigen (EBNA)3C is an immortalizing oncoprotein with similar properties to adenovirus E1A and papillomavirus E7. Oncogene 13:2541–2549
    [Google Scholar]
  27. Robertson E. S., Grossman S., Johannsen E., Miller C., Lin J., Tomkinson B., Kieff E. 1995; Epstein-Barr virus nuclear protein 3C modulates transcription through interaction with the sequence-specific DNA-binding protein J k . Journal of Virology 69:3108–3116
    [Google Scholar]
  28. Robertson E. S., Lin J., Kieff E. 1996; The amino-terminal domains of Epstein-Barr virus nuclear proteins 3A, 3B and 3C interact with RBPJK. Journal of Virology 70:3068–3074
    [Google Scholar]
  29. Rooney C. M., Brimmell M., Buschle M., Allan G., Farrell P. J., Kolman J. L. 1992; regulation of Epstein-Barr virus latent-cycle promoter activity in B lymphocytes. Journal of Virology 66:496–504
    [Google Scholar]
  30. Silins S. L., Sculley T. B. 1994; Modulation of vimentin, the CD40 activation antigen and Burkitt's lymphoma antigen (CD77) by the Epstein-Barr virus nuclear antigen EBNA-4. Virology 202:16–24
    [Google Scholar]
  31. Sinclair A. J., Palmero I., Peters G., Farrell P. J. 1994; EBNA-2 and EBNA-LP cooperate to cause G0 to G1 transition during immortalization of resting human B lymphocytes by Epstein-Barr virus. EMBO Journal 13:3321–3328
    [Google Scholar]
  32. Sung N. S., Kenney S., Gutsch D., Pagano J. S. 1991; EBNA-2 transactivates a lymphoid-specific enhancer in the BamHI C promoter of Epstein-Barr virus. Journal of Virology 65:2164–2169
    [Google Scholar]
  33. Tomkinson B., Robertson E., Kieff E. 1993; Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation. Journal of Virology 67:2014–2025
    [Google Scholar]
  34. Waltzer L., Bourillot P. Y., Sergeant A., Manet E. 1995; RBP-JK repression activity is mediated by a co-repressor and antagonized by the Epstein-Barr virus transcription factor EBNA2. Nucleic Acids Research 23:4939–4945
    [Google Scholar]
  35. Waltzer L., Logeat F., Brou C., Israel A., Sergeant A., Manet E. 1994; The human JK recombination signal sequence binding protein (RBP-J k ) targets the Epstein-Barr virus EBNA2 protein to its DNA responsive elements. EMBO Journal 13:5633–5638
    [Google Scholar]
  36. Waltzer L., Perricaudet M., Sergeant A., Manet E. 1996; Epstein-Barr virus EBNA3A and EBNA3C proteins both repress RBP-JK- EBNA2-activated transcription by inhibiting the binding of RBP-JK to DNA. Journal of Virology 70:5909–5915
    [Google Scholar]
  37. Wang F., Gregory C., Sample C., Rowe M., Liebowitz D., Murray R., Rickinson A., Kieff E. 1990a; Epstein-Barr virus latent membrane protein (LMP1) and nuclear antigen 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. Journal of Virology 64:2309–2318
    [Google Scholar]
  38. Wang F., Tsang S.-F., Kurilla M. G., Cohen J. I., Kieff E. 1990b; Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1. Journal of Virology 64:3407–3416
    [Google Scholar]
  39. Webster N., Green S., Tasset D., Ponglikitmongkol M., Chambon P. 1989; The transcriptional activation function located in the hormone-binding domain of the human oestrogen receptor is not encoded in a single exon. EMBO Journal 8:1441–1446
    [Google Scholar]
  40. Woisetchlaeger M., Yandava C. N., Furmanski L. A., Strominger J. L., Speck S. 1990; Promoter switching in Epstein-Barr virus during the initial stages of infection of B lymphocytes. 87:1725–1729
    [Google Scholar]
  41. Yalamanchili R., Tong X., Grossman S., Johannsen E., Mosialos G., Kieff E. 1994; Genetic and biochemical evidence that EBNA2 interaction with a 63-kDa cellular GTG-binding protein is essential for B lymphocyte growth transformation by EBV. Virology 204:634–641
    [Google Scholar]
  42. Zhao B., Marshall D. R., Sample C. E. 1996; A conserved domain of the Epstein-Barr virus nuclear antigen 3A and 3C binds to a discrete domain of JK. Journal of Virology 70:4228–4236
    [Google Scholar]
  43. Zimber-Strobl U., Suentzenich K.-O., Laux G., Eick D., Cordier M., Calender A., Billaud M., Lenoir G. M., Bornkamm G. W. 1991; Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene. Journal of Virology 65:415–423
    [Google Scholar]
  44. Zimber-Strobl U., Strobl L. J., Meitinger C., Hinrichs R., Sakai T., Furukawa T., Honjo T., Bornkamm G. 1994; Epstein-Barr virus nuclear antigen 2 exerts its transactivating function through interaction with recombination signal binding protein RBP-J k , the homologue of Drosophila Suppressor of Hairless . EMBO Journal 13:4973–4982
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-79-2-363
Loading
/content/journal/jgv/10.1099/0022-1317-79-2-363
Loading

Data & Media loading...

Most cited Most Cited RSS feed