Epstein–Barr virus protein kinase BGLF4 interacts with viral transactivator BZLF1 and regulates its transactivation activity Free

Abstract

BGLF4 is a serine/threonine protein kinase encoded by Epstein–Barr virus. One of the physiological substrates of BGLF4 is viral transactivator BZLF1. In the present study, it was demonstrated that alanine substitution of the serine residue at position 209 (S209A) in BZLF1 eliminated phosphorylation of the protein by BGLF4 . The S209A mutation in BZLF1, as well as a K102I mutation in BGLF4, which inactivated catalytic activity of the viral kinase, also inhibited formation of a stable BGLF4–BZLF1 complex and downregulation of BZLF1 autotransactivation activity mediated by BGLF4. These results indicate that formation of a stable complex of BGLF4–BZLF1 enables downregulation of BZLF1 autoregulation activity and it appears that BGLF4 phosphorylation of BZLF1 may be involved in these processes.

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2009-07-01
2024-03-28
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References

  1. Asai R., Kato A., Kato K., Kanamori-Koyama M., Sugimoto K., Sairenji T., Nishiyama Y., Kawaguchi Y. 2006; Epstein–Barr virus protein kinase BGLF4 is a virion tegument protein that dissociates from virions in a phosphorylation-dependent process and phosphorylates the viral immediate-early protein BZLF1. J Virol 80:5125–5134 [CrossRef]
    [Google Scholar]
  2. Chee M. S., Lawrence G. L., Barrell B. G. 1989; Alpha-, beta- and gammaherpesviruses encode a putative phosphotransferase. J Gen Virol 70:1151–1160 [CrossRef]
    [Google Scholar]
  3. Chen M. R., Chang S. J., Huang H., Chen J. Y. 2000; A protein kinase activity associated with Epstein–Barr virus BGLF4 phosphorylates the viral early antigen EA-D in vitro. J Virol 74:3093–3104 [CrossRef]
    [Google Scholar]
  4. Flemington E., Speck S. H. 1990; Autoregulation of Epstein–Barr virus putative lytic switch gene BZLF1. J Virol 64:1227–1232
    [Google Scholar]
  5. Gershburg E., Pagano J. S. 2002; Phosphorylation of the Epstein–Barr virus (EBV) DNA polymerase processivity factor EA-D by the EBV-encoded protein kinase and effects of the l-riboside benzimidazole 1263W94. J Virol 76:998–1003 [CrossRef]
    [Google Scholar]
  6. Gershburg E., Marschall M., Hong K., Pagano J. S. 2004; Expression and localization of the Epstein–Barr virus-encoded protein kinase. J Virol 78:12140–12146 [CrossRef]
    [Google Scholar]
  7. Gershburg E., Raffa S., Torrisi M. R., Pagano J. S. 2007; Epstein–Barr virus-encoded protein kinase (BGLF4) is involved in production of infectious virus. J Virol 81:5407–5412 [CrossRef]
    [Google Scholar]
  8. Izumiya Y., Izumiya C., Van Geelen A., Wang D. H., Lam K. S., Luciw P. A., Kung H. J. 2007; Kaposi's sarcoma-associated herpesvirus-encoded protein kinase and its interaction with K-bZIP. J Virol 81:1072–1082 [CrossRef]
    [Google Scholar]
  9. Johannsen E., Luftig M., Chase M. R., Weicksel S., Cahir-McFarland E., Illanes D., Sarracino D., Kieff E. 2004; Proteins of purified Epstein–Barr virus. Proc Natl Acad Sci U S A 101:16286–16291 [CrossRef]
    [Google Scholar]
  10. 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 [CrossRef]
    [Google Scholar]
  11. Kato K., Kawaguchi Y., Tanaka M., Igarashi M., Yokoyama A., Matsuda G., Kanamori M., Nakajima K., Nishimura Y. other authors 2001; Epstein–Barr virus-encoded protein kinase BGLF4 mediates hyperphosphorylation of cellular elongation factor 1 δ (EF-1 δ ): EF-1 δ is universally modified by conserved protein kinases of herpesviruses in mammalian cells. J Gen Virol 82:1457–1463
    [Google Scholar]
  12. 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 [CrossRef]
    [Google Scholar]
  13. Kato A., Yamamoto M., Ohno T., Kodaira H., Nishiyama Y., Kawaguchi Y. 2005; Identification of proteins phosphorylated directly by the Us3 protein kinase encoded by herpes simplex virus 1. J Virol 79:9325–9331 [CrossRef]
    [Google Scholar]
  14. Kato A., Yamamoto M., Ohno T., Tanaka M., Sata T., Nishiyama Y., Kawaguchi Y. 2006; Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31. J Virol 80:1476–1486 [CrossRef]
    [Google Scholar]
  15. Kato A., Tanaka M., Yamamoto M., Asai R., Sata T., Nishiyama Y., Kawaguchi Y. 2008; Identification of a physiological phosphorylation site of the herpes simplex virus 1-encoded protein kinase Us3 which regulates its optimal catalytic activity in vitro and influences its function in infected cells. J Virol 82:6172–6189 [CrossRef]
    [Google Scholar]
  16. Kato A., Arii J., Shiratori I., Akashi H., Arase H., Kawaguchi Y. 2009; Herpes simplex virus 1 protein kinase Us3 phosphorylates viral envelope glycoprotein B and regulates its expression on the cell surface. J Virol 83:250–261 [CrossRef]
    [Google Scholar]
  17. Kawaguchi Y., Kato K. 2003; Protein kinases conserved in herpesviruses potentially share a function mimicking the cellular protein kinase cdc2. Rev Med Virol 13:331–340 [CrossRef]
    [Google Scholar]
  18. Kawaguchi Y., Nakajima K., Igarashi M., Morita T., Tanaka M., Suzuki M., Yokoyama A., Matsuda G., Kato K. other authors 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 [CrossRef]
    [Google Scholar]
  19. Kawaguchi Y., Tanaka M., Yokoymama A., Matsuda G., Kato K., Kagawa H., Hirai K., Roizman B. 2001; Herpes simplex virus 1 alpha regulatory protein ICP0 functionally interacts with cellular transcription factor BMAL1. Proc Natl Acad Sci U S A 98:1877–1882
    [Google Scholar]
  20. Kawaguchi Y., Kato K., Tanaka M., Kanamori M., Nishiyama Y., Yamanashi Y. 2003; Conserved protein kinases encoded by herpesviruses and cellular protein kinase cdc2 target the same phosphorylation site in eukaryotic elongation factor 1 δ . J Virol 77:2359–2368 [CrossRef]
    [Google Scholar]
  21. Kenyon T. K., Cohen J. I., Grose C. 2002; Phosphorylation by the varicella-zoster virus ORF47 protein serine kinase determines whether endocytosed viral gE traffics to the trans -Golgi network or recycles to the cell membrane. J Virol 76:10980–10993 [CrossRef]
    [Google Scholar]
  22. Kieff E. D., Rickinson A. B. 2007; Epstein–Barr virus and its replication. In Fields Virology , 5th edn. pp 2603–2654Edited by Knipe D. M., Howley P. M., Griffin D. E., Lamb R. A., Martin M. A., Roizman B., Straus S. E. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  23. Kudoh A., Daikoku T., Ishimi Y., Kawaguchi Y., Shirata N., Iwahori S., Isomura H., Tsurumi T. 2006; Phosphorylation of MCM4 at sites inactivating DNA helicase activity of the MCM4–MCM6–MCM7 complex during Epstein–Barr virus productive replication. J Virol 80:10064–10072 [CrossRef]
    [Google Scholar]
  24. Lee C. P., Chen J. Y., Wang J. T., Kimura K., Takemoto A., Lu C. C., Chen M. R. 2007; Epstein–Barr virus BGLF4 kinase induces premature chromosome condensation through activation of condensin and topoisomerase II. J Virol 81:5166–5180 [CrossRef]
    [Google Scholar]
  25. Mocarski E. S., Shenk T., Pass R. T. 2007; Cytomegaloviruses. In Fields Virology . , 5th edn. pp 2701–2772Edited by Knipe D. M., Howley P. M., Griffin D. E., Lamb R. A., Martin M. A., Roizman B., Straus S. E. Philadelphia, PA: Lippincott Williams & Wilkins;
  26. Roizman B., Knipe D. M., Whitley R. J. 2007; Herpes simplex viruses. In Fields Virology , 5th edn. pp 2501–2601Edited by Knipe D. M., Howley P. M., Griffin D. E., Lamb R. A., Martin M. A., Roizman B., Straus. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  27. Sambrook J., Russell D. W. 2001; Site-specific mutagenesis by overlap extension. In Molecular Cloning , 3rd edn.pp. 13.36–13.39 Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  28. Smith R. F., Smith T. F. 1989; Identification of new protein kinase-related genes in three herpesviruses, herpes simplex virus, varicella-zoster virus, and Epstein–Barr virus. J Virol 63:450–455
    [Google Scholar]
  29. Wang J. T., Yang P. W., Lee C. P., Han C. H., Tsai C. H., Chen M. R. 2005; Detection of Epstein–Barr virus BGLF4 protein kinase in virus replication compartments and virus particles. J Gen Virol 86:3215–3225 [CrossRef]
    [Google Scholar]
  30. Yin Q., Jupiter K., Flemington E. K. 2004; The Epstein–Barr virus transactivator Zta binds to its own promoter and is required for full promoter activity during anti-Ig and TGF- β 1 mediated reactivation. Virology 327:134–143 [CrossRef]
    [Google Scholar]
  31. Yokoyama A., Tanaka M., Matsuda G., Kato K., Kanamori M., Kawasaki H., Hirano H., Kitabayashi I., Ohki M. other authors 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 [CrossRef]
    [Google Scholar]
  32. Yuan J., Cahir-McFarland E., Zhao B., Kieff E. 2006; Virus and cell RNAs expressed during Epstein–Barr virus replication. J Virol 80:2548–2565 [CrossRef]
    [Google Scholar]
  33. 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 [CrossRef]
    [Google Scholar]
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