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1887

Journal of General Virology header logo Journal of General Virology

Volume 88, Issue 10

Post-translational modifications of Epstein–Barr virus oncogene-encoded polypeptide No Access

Abstract

Epstein–Barr virus is associated with several human lymphomas and carcinomas, and its oncogene encodes a protein that is thought to play an important role in carcinogenesis. A BARF1 recombinant adenovirus expression system, which led us to discover the macromolecular size of the cleaved and secreted form of the BARF1 protein in the native state and its mitogenic capacity on various cell lines in culture, was used further to investigate the structure and maturation of the BARF1 protein. We recently reported biophysical studies that showed dimer-based oligomerization of the BARF1 polypeptide. Here, new data are presented that confirm post-translational modifications predicted from the BARF1 sequence: phosphorylation on serine and threonine, and - and -glycosylation. The - and -glycans were partially characterized and it was demonstrated that both modifications are required for active secretion of the BARF1 protein via the classical pathway.

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2007-10-01
2026-01-19

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References

  1. Blom N., Gammeltoft S., Brunak S. 1999; Sequence- and structure-based prediction of eukaryotic protein phosphorylation sites. J Mol Biol 294:1351–1362 [CrossRef]
     [Google Scholar]
  2. Cals M. M., Guenzi S., Carelli S., Simmen T., Sparvoli A., Sitia R. 1996; IgM polymerization inhibits the Golgi-mediated processing of the mu-chain carboxy-terminal glycans. Mol Immunol 33:15–24 [CrossRef]
     [Google Scholar]
  3. Carpentier M., Morelle W., Coddeville B., Pons A., Masson M., Mazurier J., Legrand D. 2005; Nucleolin undergoes partial N - and O -glycosylations in the extranuclear cell compartment. Biochemistry 44:5804–5815 [CrossRef]
     [Google Scholar]
  4. Cohen J. I., Lekstrom K. 1999; Epstein–Barr virus BARF1 protein is dispensable for B-cell transformation and inhibits alpha interferon secretion from mononuclear cells. J Virol 73:7627–7632
     [Google Scholar]
  5. Combet C., Blanchet C., Geourjon C., Deleage G. 2000; nps@: network protein sequence analysis. Trends Biochem Sci 25:147–150 [CrossRef]
     [Google Scholar]
  6. de Turenne-Tessier M., Jolicoeur P., Ooka T. 1997; Expression of the protein encoded by Epstein–Barr virus (EBV) BARF1 open reading frame from a recombinant adenovirus system. Virus Res 52:73–85 [CrossRef]
     [Google Scholar]
  7. de Turenne-Tessier M., Jolicoeur P., Middeldorp J. M., Ooka T. 2005; Expression and analysis of the Epstein–Barr virus BARF1-encoded protein from a tetracycline-regulatable adenovirus system. Virus Res 109:9–18 [CrossRef]
     [Google Scholar]
  8. Decaussin G., Sbih-Lammali F., de Turenne-Tessier M., Bouguermouh A., Ooka T. 2000; Expression of BARF1 gene encoded by Epstein–Barr virus in nasopharyngeal carcinoma biopsies. Cancer Res 60:5584–5588
     [Google Scholar]
  9. Evans A. G., Moorman N. J., Willer D. O., Speck S. H. 2006; The M4 gene of γ HV68 encodes a secreted glycoprotein and is required for the efficient establishment of splenic latency. Virology 344:520–531 [CrossRef]
     [Google Scholar]
  10. Julenius K., Molgaard A., Gupta R., Brunak S. 2005; Prediction, conservation analysis and structural characterization of mammalian mucin-type O -glycosylation sites. Glycobiology 15:153–164
     [Google Scholar]
  11. Luo B., Wang Y., Wang X. F., Liang H., Yan L. P., Huang B. H., Zhao P. 2005; Expression of Epstein–Barr virus genes in EBV-associated gastric carcinomas. World J Gastroenterol 11:629–633 [CrossRef]
     [Google Scholar]
  12. Maley F., Trimble R. B., Tarentino A. L., Plummer T. H., Jr. 1989; Characterization of glycoproteins and their associated oligosaccharides through the use of endoglycosidases. Anal Biochem 180:195–204 [CrossRef]
     [Google Scholar]
  13. Mardassi H., Gonin P., Gagnon C. A., Massie B., Dea S. 1998; A subset of porcine reproductive and respiratory syndrome virus GP3 glycoprotein is released into the culture medium of cells as a non-virion-associated and membrane-free (soluble) form. J Virol 72:6298–6306
     [Google Scholar]
  14. Meads M. B., Medveczky P. G. 2004; Kaposi's sarcoma-associated herpesvirus encoded viral interleukin-6 is secreted and modified differently than human interleukin-6: evidence for a unique autocrine signaling mechanism. J Biol Chem 279:51793–51803 [CrossRef]
     [Google Scholar]
  15. Mitra N., Sinha S., Ramya T. N. C., Surolia A. 2006; N -linked oligosaccharides as outfitters for glycoprotein folding, form and function. Trends Biochem Sci 31:156–163 [CrossRef]
     [Google Scholar]
  16. Nagano M., Stübiger G., Marchetti M., Gmeiner G., Allmaier G., Reichel C. 2005; Detection of isoforms of recombinant human erythropoietin by various plant lectins after isoelectric focusing. Electrophoresis 26:1633–1645 [CrossRef]
     [Google Scholar]
  17. Ng A., Tscharke D. C., Reading P. C., Smith G. L. 2001; The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence. J Gen Virol 82:2095–2105
     [Google Scholar]
  18. Ooka T. 2005; Biological role of the BARF1 gene encoded by Epstein–Barr virus. In Epstein–Barr Virus pp 613–630 Edited by Robertson E. S. Norfolk, UK: Caister Academic Press;
     [Google Scholar]
  19. Pager C. T., Wurth M. A., Dutch R. E. 2004; Subcellular localization and calcium and pH requirements for proteolytic processing of the Hendra virus fusion protein. J Virol 78:9154–9163 [CrossRef]
     [Google Scholar]
  20. Ressing M. E., van Leeuwen D., Verreck F. A., Keating S., Gomez R., Franken K. L., Ottenhoff T. H., Spriggs M., Schumacher T. N. other authors 2005; Epstein–Barr virus gp42 is posttranslationally modified to produce soluble gp42 that mediates HLA class II immune evasion. J Virol 79:841–852 [CrossRef]
     [Google Scholar]
  21. Rudd P. M., Dwek R. A. 1997; Glycosylation: heterogeneity and the 3D structure of proteins. Crit Rev Biochem Mol Biol 32:1–100 [CrossRef]
     [Google Scholar]
  22. Salazar C., Höfer T. 2007; Versatile regulation of multisite protein phosphorylation by the order of phosphate processing and protein-protein interactions. FEBS J 274:1046–1061 [CrossRef]
     [Google Scholar]
  23. Sall A., Caserta S., Jolicoeur P., Franqueville L., de Turenne-Tessier M., Ooka T. 2004; Mitogenic activity of Epstein–Barr virus-encoded BARF1 protein. Oncogene 23:4938–4944 [CrossRef]
     [Google Scholar]
  24. Seto E., Yang L., Middeldorp J., Sheen T. S., Chen J. Y., Fukayama M., Eizuru Y., Ooka T., Takada K. 2005; Epstein–Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression. J Med Virol 76:82–88 [CrossRef]
     [Google Scholar]
  25. Spiro R. G. 2002; Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology 12:43R–56R [CrossRef]
     [Google Scholar]
  26. Strockbine L. D., Cohen J. I., Farrah T., Lyman S. D., Wagener F., DuBose R. F., Armitage R. J., Spriggs M. K. 1998; The Epstein–Barr virus BARF1 gene encodes a novel, soluble colony-stimulating factor-1 receptor. J Virol 72:4015–4021
     [Google Scholar]
  27. Tanner J. E., Wei M. X., Alfieri C., Ahmad A., Taylor P., Ooka T., Menezes J. 1997; Antibody and antibody-dependent cellular cytotoxicity responses against the Bam H1 A rightward open-reading frame-1 protein of Epstein–Barr virus (EBV) in EBV-associated disorders. J Infect Dis 175:38–46 [CrossRef]
     [Google Scholar]
  28. Tarbouriech N., Ruggiero F., de Turenne-Tessier M., Ooka T., Burmeister W. P. 2006; Structure of the Epstein–Barr virus oncogene BARF1. J Mol Biol 359:667–678 [CrossRef]
     [Google Scholar]
  29. Tsuiji H., Takasaki S., Sakamoto M., Irimura T., Hirohashi S. 2003; Aberrant O -glycosylation inhibits stable expression of dysadherin, a carcinoma-associated antigen, and facilitates cell-cell adhesion. Glycobiology 13:521–527 [CrossRef]
     [Google Scholar]
  30. Van den Steen P., Rudd P. M., Dwek R. A., Opdenakker G. 1998; Concepts and principles of O -linked glycosylation. Crit Rev Biochem Mol Biol 33:151–208 [CrossRef]
     [Google Scholar]
  31. Wahl-Jensen V., Kurz S. K., Hazelton P. R., Schnittler H. J., Stroher U., Burton D. R., Feldmann H. 2005; Role of Ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages. J Virol 79:2413–2419 [CrossRef]
     [Google Scholar]
  32. Wang L., Tam J. P., Liu D. X. 2006a; Biochemical and functional characterization of Epstein–Barr virus-encoded BARF1 protein: interaction with human hTid1 protein facilitates its maturation and secretion. Oncogene 25:4320–4331 [CrossRef]
     [Google Scholar]
  33. Wang Q., Tsao S. W., Ooka T., Nicholls J. M., Cheung H. W., Fu S., Wong Y. C., Wang X. 2006b; Anti-apoptotic role of BARF1 in gastric cancer cells. Cancer Lett 238:90–103 [CrossRef]
     [Google Scholar]
  34. Young L. S., Rickinson A. B. 2004; Epstein–Barr virus: 40 years on. Nat Rev Cancer 4:757–768 [CrossRef]
     [Google Scholar]
  35. zur Hausen A., Brink A. A., Craanen M. E., Middeldorp J. M., Meijer C. J., van den Brule A. J. 2000; Unique transcription pattern of Epstein–Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene. Cancer Res 60:2745–2748
     [Google Scholar]
/content/journal/jgv/10.1099/vir.0.83058-0
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Post-translational modifications of Epstein–Barr virus BARF1 oncogene-encoded polypeptide
J. Gen. Virol. 88, 2656 (2007); https://doi.org/10.1099/vir.0.83058-0
/content/journal/jgv/10.1099/vir.0.83058-0
/content/journal/jgv/10.1099/vir.0.83058-0
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