1887

Abstract

Microarray analysis covering most of the annotated RNAs in the human genome identified a panel of genes induced by the Epstein–Barr virus (EBV) EBNA-2 transcription factor in the EREB2.5 human B-lymphoblastoid cell line without the need for any intermediate protein synthesis. Previous data indicating that PIK3R1 RNA (the regulatory subunit of PI3-kinase) was induced were confirmed, but it is now shown that it is the p55 regulatory subunit that is induced. Several EBV-immortalized lymphoblastoid cell lines were shown to express p55. Expression of PI3-kinase p85 regulatory and p110 catalytic subunits was not regulated by EBNA-2. Proliferation of EREB2.5 lymphoblastoid cells was inhibited by RNAi knock-down of p55 protein expression, loss of p55 being accompanied by an increase in apoptosis. p55 is thus a functional target of EBNA2 in EREB2.5 cells and the specific regulation of p55 by EBV will provide an opportunity to investigate the physiological function of p55 in this human cell line.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82128-0
2006-10-01
2024-11-13
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/10/2859.html?itemId=/content/journal/jgv/10.1099/vir.0.82128-0&mimeType=html&fmt=ahah

References

  1. Ali K., Bilancio A., Thomas M. & 14 other authors 2004; Essential role for the p110 δ phosphoinositide 3-kinase in the allergic response. Nature 431:1007–1011 [CrossRef]
    [Google Scholar]
  2. Brennan P., Mehl A. M., Jones M., Rowe M. 2002; Phosphatidylinositol 3-kinase is essential for the proliferation of lymphoblastoid cells. Oncogene 21:1263–1271 [CrossRef]
    [Google Scholar]
  3. Castoria G., Migliaccio A., Bilancio A. & 7 other authors 2001; PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells. EMBO J 20:6050–6059 [CrossRef]
    [Google Scholar]
  4. Dawson C. W., Tramountanis G., Eliopoulos A. G., Young L. S. 2003; Epstein-Barr virus latent membrane protein 1 (LMP1) activates the phosphatidylinositol 3-kinase/Akt pathway to promote cell survival and induce actin filament remodeling. J Biol Chem 278:3694–3704 [CrossRef]
    [Google Scholar]
  5. End P., Gout I., Fry M. J., Panayotou G., Dhand R., Yonezawa K., Kasuga M., Waterfield M. D. 1993; A biosensor approach to probe the structure and function of the p85 α subunit of the phosphatidylinositol 3-kinase complex. J Biol Chem 268:10066–10075
    [Google Scholar]
  6. Fruman D. A., Snapper S. B., Yballe C. M., Alt F. W., Cantley L. C. 1999a; Phosphoinositide 3-kinase knockout mice: role of p85alpha in B cell development and proliferation. Biochem Soc Trans 27:624–629
    [Google Scholar]
  7. Fruman D. A., Snapper S. B., Yballe C. M., Davidson L., Yu J. Y., Alt F. W., Cantley L. C. 1999b; Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85 α . Science 283:393–397 [CrossRef]
    [Google Scholar]
  8. Fukuda M., Longnecker R. 2004; Latent membrane protein 2A inhibits transforming growth factor- β 1-induced apoptosis through the phosphatidylinositol 3-kinase/Akt pathway. J Virol 78:1697–1705 [CrossRef]
    [Google Scholar]
  9. Gout I., Dhand R., Hiles I. D. & 9 other authors 1993; The GTPase dynamin binds to and is activated by a subset of SH3 domains. Cell 75:25–36 [CrossRef]
    [Google Scholar]
  10. Inukai K., Anai M., Van Breda E. & 9 other authors 1996; A novel 55-kDa regulatory subunit for phosphatidylinositol 3-kinase structurally similar to p55PIK is generated by alternative splicing of the p85 α gene. J Biol Chem 271:5317–5320 [CrossRef]
    [Google Scholar]
  11. Inukai K., Funaki M., Ogihara T. & 12 other authors 1997; p85 α gene generates three isoforms of regulatory subunit for phosphatidylinositol 3-kinase (PI 3-kinase), p50 α , p55 α , and p85 α , with different PI 3-kinase activity elevating responses to insulin. J Biol Chem 272:7873–7882 [CrossRef]
    [Google Scholar]
  12. Inukai K., Funaki M., Nawano M. & 10 other authors 2000; The N-terminal 34 residues of the 55 kDa regulatory subunits of phosphoinositide 3-kinase interact with tubulin. Biochem J 346:483–489 [CrossRef]
    [Google Scholar]
  13. Inukai K., Funaki M., Anai M. & 11 other authors 2001; Five isoforms of the phosphatidylinositol 3-kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations. FEBS Lett 490:32–38 [CrossRef]
    [Google Scholar]
  14. Kaiser C., Laux G., Eick D., Jochner N., Bornkamm G. W., Kempkes B. 1999; The proto-oncogene c- myc is a direct target gene of Epstein-Barr virus nuclear antigen 2. J Virol 73:4481–4484
    [Google Scholar]
  15. Kempkes B., Spitkovsky D., Jansen-Durr 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 J 14:88–96
    [Google Scholar]
  16. Kieff E., Rickinson A. B. 2001; Epstein-Barr virus and its replication. In Fields Virology , 4th edn. pp  2511–2573 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  17. Mann K. P., Staunton D., Thorley-Lawson D. A. 1985; Epstein-Barr virus-encoded protein found in plasma membrane in transformed cells. J Virol 55:710–720
    [Google Scholar]
  18. Okada T., Maeda A., Iwamatsu A., Gotoh K., Kurosaki T. 2000; BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation. Immunity 13:817–827 [CrossRef]
    [Google Scholar]
  19. Okamoto T., Namikawa K., Asano T., Takaoka K., Kiyama H. 2004; Differential regulation of the regulatory subunits for phosphatidylinositol 3-kinase in response to motor nerve injury. Brain Res Mol Brain Res 131:119–125 [CrossRef]
    [Google Scholar]
  20. Okkenhaug K., Vanhaesebroeck B. 2003; PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol 3:317–330 [CrossRef]
    [Google Scholar]
  21. Portis T., Longnecker R. 2004; Epstein–Barr virus (EBV) LMP2A mediates B-lymphocyte survival through constitutive activation of the Ras/PI3K/Akt pathway. Oncogene 23:8619–8628 [CrossRef]
    [Google Scholar]
  22. Raftopoulou M., Hall A. 2004; Cell migration: Rho GTPases lead the way. Dev Biol 265:23–32 [CrossRef]
    [Google Scholar]
  23. Scholle F., Bendt K. M., Raab-Traub N. 2000; Epstein-Barr virus LMP2A transforms epithelial cells, inhibits cell differentiation, and activates Akt. J Virol 74:10681–10689 [CrossRef]
    [Google Scholar]
  24. Sinclair A. J., Farrell P. J. 1995; Host cell requirements for efficient infection of quiescent primary B lymphocytes by Epstein-Barr virus. J Virol 69:5461–5468
    [Google Scholar]
  25. Spender L. C., Cornish G. H., Sullivan A., Farrell P. J. 2002; Expression of transcription factor AML-2 (RUNX3, CBF α -3) is induced by Epstein-Barr virus EBNA-2 and correlates with the B-cell activation phenotype. J Virol 76:4919–4927 [CrossRef]
    [Google Scholar]
  26. Spender L. C., Whiteman H. J., Karstegl C. E., Farrell P. J. 2005; Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells. Oncogene 24:1873–1881 [CrossRef]
    [Google Scholar]
  27. Swart R., Ruf I. K., Sample J., Longnecker R. 2000; Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-kinase/Akt pathway. J Virol 74:10838–10845 [CrossRef]
    [Google Scholar]
  28. Terauchi Y., Tsuji Y., Satoh S. & 30 other authors 1999; Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 α subunit of phosphoinositide 3-kinase. Nat Genet 21:230–235 [CrossRef]
    [Google Scholar]
  29. Tsai E.-M., Wang S.-C., Lee J.-N., Hung M.-C. 2001; Akt activation by estrogen in estrogen receptor-negative breast cancer cells. Cancer Res 61:8390–8392
    [Google Scholar]
  30. Ueki K., Algenstaedt P., Mauvais-Jarvis F., Kahn C. R. 2000; Positive and negative regulation of phosphoinositide 3-kinase-dependent signaling pathways by three different gene products of the p85 α regulatory subunit. Mol Cell Biol 20:8035–8046 [CrossRef]
    [Google Scholar]
  31. Ueki K., Fruman D. A., Brachmann S. M., Tseng Y.-H., Cantley L. C., Kahn C. R. 2002; Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival. Mol Cell Biol 22:965–977 [CrossRef]
    [Google Scholar]
  32. Wilkinson S., Paterson H. F., Marshall C. J. 2005; Cdc42–MRCK and Rho–ROCK signalling cooperate in myosin phosphorylation and cell invasion. Nat Cell Biol 7:255–261 [CrossRef]
    [Google Scholar]
  33. Zhao B., Maruo S., Cooper A., Chase M. R., Johannsen E., Kieff E., Cahir-McFarland E. 2006; RNAs induced by Epstein–Barr virus nuclear antigen 2 in lymphoblastoid cell lines. Proc Natl Acad Sci U S A 103:1900–1905 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.82128-0
Loading
/content/journal/jgv/10.1099/vir.0.82128-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error