1887

Abstract

The hepatitis B virus × protein (HBx) is suggested to regulate transcription by stimulation of intracellular signalling pathways. We have analysed the effects of HBx on activation of the MAP kinase (Erk) and JNK/SAPK signalling pathways and confirm a stimulation of the Erk/MAP kinase in quiescent cells. However, a substantial Erk-independent activation of AP-1, and phosphorylation of c-Jun (serine-63), but not Erk-2, was induced by HBx in dividing, serum-maintained cells. These data suggest that HBx promiscuously activates Erk and JNK responsive pathways and that its overall effect on signalling may be influenced by external mitogenic stimuli.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-79-11-2737
1998-11-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/79/11/9820149.html?itemId=/content/journal/jgv/10.1099/0022-1317-79-11-2737&mimeType=html&fmt=ahah

References

  1. Antunovic J., Lemieux N., Cromlish J. A. 1993; The 17 kDa HBx protein encoded by hepatitis B virus interacts with the activation domains of Oct 1, and functions as a coactivator in the activation and repression of a human U6 promoter. Cellular and Molecular Biology Research 39:463–482
    [Google Scholar]
  2. Benn J., Schneider R. J. 1994; The hepatitis B virus HBx protein activates Ras-GTP complex formation and establishes a Ras, Raf, MAP kinase signalling cascade. Proceedings of the National Academy of Sciences, USA 91:10350–10354
    [Google Scholar]
  3. Benn J., Schneider R. J. 1995; Hepatitis B virus HBx protein deregulates cell cycle checkpoint controls. Proceedings of the National Academy of Sciences, USA 92:11215–11219
    [Google Scholar]
  4. Benn J., Su F., Doria M., Schneider R. J. 1996; Hepatitis B virus HBx protein induces transcription factor AP-1 by activation of extracellular signal regulated and c-Jun N-terminal mitogen activated protein kinases. Journal of Virology 70:4978–4985
    [Google Scholar]
  5. Bohman D., Bos J. T., Admon A., Nishimura T., Voght P. K., Tijan R. 1987; Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science 238:1386–1392
    [Google Scholar]
  6. Coso O. A., Chiariello M., Yu G. J. C., Teramoro H., Crespo P., Xu N., Miki T., Gutkind J. S. 1995a; The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signalling pathway. Cell 81:1137–1146
    [Google Scholar]
  7. Coso O. A., Chiariello M., Kalinec G., Kyriakis J. M., Woodgett J., Gutkind J. S. 1995b; Transforming G protein-coupled receptors potently activate JNK (SAPK) - evidence for a divergence from the tyrosine kinase signalling pathway. Journal of Biological Chemistry 270:5620–5626
    [Google Scholar]
  8. Cross J. C., Wen P., Rutter W. J. 1993; Transactivation by the hepatitis B virus X protein is promiscuous and dependent on mitogen activated cellular serine/threonine kinases. Proceedings of the National Academy of Sciences, USA 90:8078–8082
    [Google Scholar]
  9. Derijard B., Hibi M., Wu I. H., Barrett T., Su B., Deng T., Karin M., Davies R. J. 1994; JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76:1026–1037
    [Google Scholar]
  10. de Vries-Smits A. M., Burgering B. M. T., Leevers S. J., Marshall C. J., Bos J. L. 1992; Involvement of p21ras in activation of extracellular signal-regulated kinase 2. Nature 357:602–604
    [Google Scholar]
  11. Doria M., Klein N., Lucito R., Schneider R. J. 1995; The hepatitis B virus HBx protein is a dual specificity cytoplasmic activator of Ras and nuclear activator of transcription factors. EMBO Journal 14:4747–4757
    [Google Scholar]
  12. Dudley D. T., Pang L., Decker S. J., Bridges A. J., Saltiel A. R. 1995; A synthetic inhibitor of the mitogen activated protein kinase cascade. Proceedings of the National Academy of Sciences, USA 92:7686–7689
    [Google Scholar]
  13. Feitelson M. A., Zhu M., Duan L. X., London W. T. 1993; Hepatitis B x antigen and p53 are associated in vitro and in liver tissues from patients with primary hepatocellular carcinoma. Oncogene 8:1109–1117
    [Google Scholar]
  14. Gille H., Sharrocks A. D., Shaw P. E. 1992; Phosphorylation of p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter. Nature 358:414–417
    [Google Scholar]
  15. Henkler F., Koshy R. 1996; Multiple functions of the hepatitis B virus X protein. Viral Hepatitis Reviews 2:143–159
    [Google Scholar]
  16. Henkler F., Waseem N., Golding M., Alison M., Koshy R. 1995; Mutant p53, but not hepatitis B virus X protein is present in hepatitis B virus related human hepatocellular carcinoma. Cancer Research 55:6084–6091
    [Google Scholar]
  17. Kekulé A. S., Lauer U., Weiss L., Hofschneider P. H., Koshy R. 1992; Trans-activation by hepatitis B virus X protein is mediated via a tumour promoter pathway. Archives of Virology Supplementum 4 63–64
    [Google Scholar]
  18. Klein N. P., Schneider R. J. 1997; Activation of Src family kinases by hepatitis B virus HBx protein and coupled signalling to Ras. Molecular and Cellular Biology 17:6427–6436
    [Google Scholar]
  19. Kyriakis J. M., Banerjee P., Nikolakaki E., Dal T., Rubie E. A., Ahman M. F., Avruch J., Woodgett J. R. 1994; The stress activated protein kinase subfamily of c-jun kinases. Nature 369:156–160
    [Google Scholar]
  20. Maguire H. F., Hoeffler J. P., Siddiqui A. 1991; HBV X protein alters the DNA binding specificity of CREB and ATF 2 by protein-protein interactions. Science 252:842–844
    [Google Scholar]
  21. Murakami S., Cheong J., Ohno S., Matsushima K., Kaneko S. 1994; Transactivation of human hepatitis B virus X protein, HBx, operates through a mechanism distinct from protein kinase C and okadaic acid activation pathways. Virology 199:243–246
    [Google Scholar]
  22. Natoli G., Avantaggiati L., Chirillo P., Puri P. L., Ianni A., Balsano C., Levrero M. 1994; Ras and raf dependent activation of c-jun transcriptional activity by the hepatitis B virus transactivator pX. Oncogene 9:2837–2843
    [Google Scholar]
  23. Pulverer B. J., Kyriakis J. M., Avruch J., Nikolakaki E., Woodgett J. R. 1991; Phosphorylation of c-jun mediated by MAP kinases. Nature 353:670–674
    [Google Scholar]
  24. Qadri I., Maguire H. F., Siddiqui A. 1995; Hepatitis B virus transactivator protein X interacts with the TATA binding protein. Proceedings of the National Academy of Sciences, USA 92:1003–1007
    [Google Scholar]
  25. Ramirez M. T., Sah V. P., Zhao X. L., Hunter J. J., Chien K. R., Brown J. H. 1997; The MEKK-JNK pathway is stimulated by the alpha1-adrenergic receptor and Ras-activation and is associated with in vitro and in vivo cardiac hypertrophy. Journal of Biological Chemistry 272:14057–14061
    [Google Scholar]
  26. Rossner M. T. 1992; Review: hepatitis B virus X gene product: a promiscuous transcriptional activator. Journal of Medical Virology 36:101–117
    [Google Scholar]
  27. Sanchez I., Hughes R. T., Mayers B. J., Yee K., Woodgett R. J., Avruch J., Kyriakis J. M., Zon L. J. 1994; Role of SAPK/ERK kinase-1 in the stress activated pathway regulating transcription factor c-Jun. Nature 372:794–798
    [Google Scholar]
  28. Schaap D., van der Wal J., Howes L. R., Marshall C. J., van Blitterswijk W. J. 1993; A dominant negative mutant of raf blocks mitogen activated protein kinase activation by growth factors and oncogenic p21ras. Journal of Biological Chemistry 27:20232–20236
    [Google Scholar]
  29. Spandau D. F., Lee C. H. 1988; Trans activation of viral enhancers by the hepatitis B virus X protein. Journal of Virology 62:427–434
    [Google Scholar]
  30. Truant R., Antunovic J., Greenblatt J., Prives C., Cromlish J. A. 1995; Direct interaction of the hepatitis B virus HBx protein with p53 leads to inhibition by HBx of p53 response element-directed transactivation. Journal of Virology 69:1851–1859
    [Google Scholar]
  31. Twu J. S., Schloemer R. H. 1987; Transcriptional transactivating function of hepatitis B virus. Journal of Virology 61:3448–3453
    [Google Scholar]
  32. Urich M., Senften M., Shaw P. E., Ballmer-Hofer K. 1997; A role for the small GTPase Rac in polyomavirus middle-T antigen-mediated activation of the serum response element and in cell transformation. Oncogene 14:1235–1241
    [Google Scholar]
  33. Valenzuela P., Quiroga M., Zaldivar J., Gray P., Rutter W. J. 1980; The nucleotide sequence of the hepatitis B viral genome and the identification of the major viral genes. In Animal Virus Genetics pp. 57–70 Fields N. B., Jaenisch R., Fox C. F. Edited by New York: Academic Press;
    [Google Scholar]
  34. Wang X. W., Forrester K., Yeh H., Feitelson M. A., Gu J. R., Harris C. C. 1994; Hepatitis B virus X protein inhibits sequence-specific DNA binding, transcriptional activity and association with transcription factor ERCC3. Proceedings of the National Academy of Sciences, USA 91:2230–2234
    [Google Scholar]
  35. Whitmarsh A. J., Davis R. J. 1996; Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. Journal of Molecular Medicine 74:589–607
    [Google Scholar]
  36. Williams J. S., Andrisani O. M. 1995; The hepatitis B virus X protein targets the basic region leucine zipper domain of CREB. Proceedings of the National Academy of Sciences, USA 92:3819–3823
    [Google Scholar]
  37. Zahm P., Hofschneider P. H., Koshy R. 1988; The HBV X ORF encodes a transactivator: a potential factor in viral hepatocarcinogenesis. Oncogene 3:169–177
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-79-11-2737
Loading
/content/journal/jgv/10.1099/0022-1317-79-11-2737
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