1887

Abstract

During human cytomegalovirus (HCMV) infection, a rapid increase in AP-1 activity is detected. In this study, activation of transcription from promoters containing AP-1-binding sites by the IE1 protein of HCMV was examined. In transient transfection assays with reporter plasmids, it was found that IE1 strongly induced AP-1-driven transcription. Cells stably expressing IE1 also showed higher levels of AP-1 activity than did control cells. IE1 expression did not raise levels of c-jun and c-fos RNA, as determined by quantitative RT-PCR. AP-1 induction by IE1 was blocked efficiently by protein kinase inhibitors in a cell type-dependent manner; for example, by staurosporine in the human microglial cell line U373MG and by H7 in the human promonocytic cell line U937. IE1-driven activation of AP-1 was increased dramatically by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1). The results of this study indicate that IE1 activates AP-1 at the post-transcriptional level and that MEKK1 may play an important role in this process.

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1999-04-01
2024-03-29
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References

  1. Angel P., Karin M. 1991; The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochimica et Biophysica Acta 1072:129–157
    [Google Scholar]
  2. Angel P., Herrlich P. A. (editors) 1994 The FOS and JUN Families of Transcription Factors Boca Raton: CRC Press;
    [Google Scholar]
  3. Asano T., Hidaka H. 1984; Vasodilatory action of HA1004 [N-(2-guanidinoethyl)-5-isoquinolinesulfonamide], a novel calcium antagonist with no effect on cardiac function. Journal of Pharmacology and Experimental Therapeutics 231:141–145
    [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. Biegalke B. J., Geballe A. P. 1991; Sequence requirements for activation of the HIV-1 LTR by human cytomegalovirus. Virology 183:381–385
    [Google Scholar]
  6. Boldogh I., AbuBakar S., Albrecht T. 1990; Activation of protooncogenes: an immediate early event in human cytomegalovirus infection. Science 247:561–564
    [Google Scholar]
  7. Boldogh I., AbuBakar S., Deng C. Z., Albrecht T. 1991; Transcriptional activation of cellular oncogenes fos, jun, and myc by human cytomegalovirus. Journal of Virology 65:1568–1571
    [Google Scholar]
  8. Boldogh I., Fons M. P., Albrecht T. 1993; Increased levels of sequence-specific DNA-binding proteins in human cytomegalovirus-infected cells. Biochemical and Biophysical Research Communications 197:1505–1510
    [Google Scholar]
  9. Cano E., Mahadevan L. C. 1995; Parallel signal processing among mammalian MAPKs. Trends in Biochemical Sciences 20:117–122
    [Google Scholar]
  10. Cherrington J. M., Mocarski E. S. 1989; Human cytomegalovirus ie1 transactivates the α promoter-enhancer via an 18-base-pair repeat element. Journal of Virology 63:1435–1440
    [Google Scholar]
  11. Courey A. J., Holtzman D. A., Jackson S. P., Tjian R. 1989; Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell 59:827–836
    [Google Scholar]
  12. Davis M. G., Kenney S. C., Kamine J., Pagano J. S., Huang E.-S. 1987; Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus. Proceedings of the National Academy of Sciences, USA 84:8642–8646
    [Google Scholar]
  13. Dérijard B., Raingeaud J., Barrett T., Wu I. H., Han J., Ulevitch R. J., Davis R. J. 1995; Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267:682–685
    [Google Scholar]
  14. Fanger G. R., Johnson N. L., Johnson G. L. 1997; MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42. EMBO Journal 16:4961–4972
    [Google Scholar]
  15. Gorman C. M., Moffat L. F., Howard B. H. 1982; Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Molecular and Cellular Biology 2:1044–1051
    [Google Scholar]
  16. Grosschedl R., Baltimore D. 1985; Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell 41:885–897
    [Google Scholar]
  17. Hagemeier C., Walker S. M., Sissons P. J. G., Sinclair J. H. 1992; The 72K IE1 and 80K IE2 proteins of human cytomegalovirus independently trans-activate the c-fos, c-myc and hsp 70 promoters via basal promoter elements. Journal of General Virology 73:2385–2393
    [Google Scholar]
  18. Hayhurst G. P., Bryant L. A., Caswell R. C., Walker S. M., Sinclair J. H. 1995; CCAAT box-dependent activation of the TATA-less human DNA polymerase α promoter by the human cytomegalovirus 72-kilodalton major immediate-early protein. Journal of Virology 69:182–188
    [Google Scholar]
  19. Hidaka H., Inagaki M., Kawamoto S., Sasari Y. 1984; Iso-quinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry 23:5036–5041
    [Google Scholar]
  20. Hirano M., Osada S., Aoki T., Hirai S., Hosaka M., Inoue J., Ohno S. 1996; MEK kinase is involved in tumor necrosis factor α-induced nf- κ b activation and degradation of I κ B-α. Journal of Biological Chemistry 271:13234–13238
    [Google Scholar]
  21. Ho W.-Z., Harouse J. M., Rando R. F., Gönczöl E., Srinivasan A., Plotkin S. A. 1990; Reciprocal enhancement of gene expression and viral replication between human cytomegalovirus and human immunodeficiency virus type 1. Journal of General Virology 71:97–103
    [Google Scholar]
  22. Ikeuchi K., Kim S., Byrn R. A., Goldring S. R., Groopman J. E. 1990; Infection of nonlymphoid cells by human immunodeficiency virus type 1 or type 2. Journal of Virology 64:4226–4231
    [Google Scholar]
  23. Karin M. 1995; The regulation of AP-1 activity by mitogen-activated protein kinases. Journal of Biological Chemistry 270:16483–16486
    [Google Scholar]
  24. Khachigian L. M., Williams A. J., Collins T. 1995; Interplay of Sp1 and Egr-1 in the proximal platelet-derived growth factor A-chain promoter in cultured vascular endothelial cells. Journal of Biological Chemistry 270:27679–27686
    [Google Scholar]
  25. Kieser A., Kilger E., Gires O., Ueffing M., Kolch W., Hammerschmidt W. 1997; Epstein–Barr virus latent membrane protein-1 triggers AP-1 activity via the c-Jun N-terminal kinase cascade. EMBO Journal 16:6478–6485
    [Google Scholar]
  26. Kim S., Yu S. S., Kim V. N. 1996; Essential role of nf- κ b in transactivation of the human immunodeficiency virus long terminal repeat by the human cytomegalovirus IE1 protein. Journal of General Virology 77:83–91
    [Google Scholar]
  27. Lafemina R. L., Pizzorno M. C., Mosca J. D., Hayward G. S. 1989; Expression of the acidic nuclear immediate-early protein (IE1) of human cytomegalovirus in stable cell lines and its preferential association with metaphase chromosomes. Virology 172:584–600
    [Google Scholar]
  28. Margolis M. J., Pajovic S., Wong E. L., Wade M., Jupp R., Nelson J. A., Azizkhan J. C. 1995; Interaction of the 72-kilodalton human cytomegalovirus IE1 gene product with E2F1 coincides with E2F-dependent activation of dihydrofolate reductase transcription. Journal of Virology 69:7759–7767
    [Google Scholar]
  29. Michelson S., Alcami J., Kim S. J., Danielpour D., Bachelerie F., Picard L., Bessia C., Paya C., Virelizier J. L. 1994; Human cytomegalovirus infection induces transcription and secretion of transforming growth factor β 1. Journal of Virology 68:5730–5737
    [Google Scholar]
  30. Miller A. D., Miller D. G., Garcia J. V., Lynch C. M. 1993; Use of retroviral vectors for gene transfer and expression. Methods in Enzymology 217:581–599
    [Google Scholar]
  31. Minden A., Lin A., McMahon M., Lange-Carter C., Dérijard B., Davis R. J., Johnson G. L., Karin M. 1994; Different activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science 266:1719–1723
    [Google Scholar]
  32. Mocarski E. S. Jr 1996; Cytomegaloviruses and their replication. In Fields Virology 3rd edn pp 2447–2492 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lippincott–Raven;
    [Google Scholar]
  33. Monick M. M., Geist L. J., Stinski M. F., Hunninghake G. W. 1992; The immediate early genes of human cytomegalovirus upregulate expression of the cellular genes myc and fos . American Journal of Respiratory Cell and Molecular Biology 7:251–256
    [Google Scholar]
  34. Muller U., Roberts M. P., Engel D. A., Doerfler W., Shenk T. 1989; Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP. Genes and Development 3:1991–2002
    [Google Scholar]
  35. Otto S. M., Sullivan-Tailyour G., Malone C. L., Stinski M. F. 1988; Subcellular localization of the major immediate early protein (IE1) of human cytomegalovirus at early times after infection. Virology 162:478–482
    [Google Scholar]
  36. Pajovic S., Wong E. L., Black A. R., Azizkhan J. L. 1997; Identification of a viral kinase that phosphorylates specific E2Fs and pocket proteins. Molecular and Cellular Biology 17:6459–6464
    [Google Scholar]
  37. Robbins P. D., Horowitz J. M., Mulligan R. C. 1990; Negative regulation of human c-fos expression by the retinoblastoma gene product. Nature 346:668–671
    [Google Scholar]
  38. Sambucetti L. C., Cherrington J. M., Wilkinson G. W., Mocarski E. S. 1989; nf- κ b activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO Journal 8:4251–4258
    [Google Scholar]
  39. Schönthal A., Srinivas S., Eckhart W. 1992; Induction of c-jun protooncogene expression and transcription factor AP-1 activity by the polyoma virus middle-sized tumor antigen. Proceedings of the National Academy of Sciences, USA 89:4972–4976
    [Google Scholar]
  40. Scully A. L., Sommer M. H., Schwartz R., Spector D. H. 1995; The human cytomegalovirus IE286-kilodalton protein interacts with an early gene promoter via site-specific DNA binding and protein–protein associations. Journal of Virology 69:6533–6540
    [Google Scholar]
  41. Soneoka Y., Cannon P. M., Ramsdale E. E., Griffiths J. C., Romano G., Kingsman S. M., Kingsman A. J. 1995; A transient three-plasmid expression system for the production of high titer retroviral vectors. Nucleic Acids Research 23:628–633
    [Google Scholar]
  42. Stenberg R. M., Fortney J., Barlow S. W., Magrane B. P., Nelson J. A., Ghazal P. 1990; Promoter-specific trans activation and repression by human cytomegalovirus immediate-early proteins involves common and unique protein domains. Journal of Virology 64:1556–1565
    [Google Scholar]
  43. Stinski M. F., Thomsen D. R., Stenberg R. M., Goldstein L. C. 1983; Organization and expression of the immediate early genes of human cytomegalovirus. Journal of Virology 46:1–14
    [Google Scholar]
  44. Tamaoki T., Nomoto H., Takahashi I., Kato Y., Morimoto M., Tomita F. 1986; Staurosporine, a potent inhibitor of phospholipid/ Ca++ dependent protein kinase. Biochemical and Biophysical Research Communications 135:397–402
    [Google Scholar]
  45. Tevethia M. J., Spector D. J., Leisure K. M., Stinski M. F. 1987; Participation of two human cytomegalovirus immediate early gene regions in transcriptional activation of adenovirus promoters. Virology 161:276–285
    [Google Scholar]
  46. Toullec D., Pianetti P., Coste H., Bellevergue P., Grand-Perret T., Ajakane M., Baudet V., Boissin P., Boursier E., Loriolle F. and others 1991; The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. Journal of Biological Chemistry 266:15771–15781
    [Google Scholar]
  47. Yurochko A. D., Kowalik T. F., Huong S. M., Huang E. S. 1995; Human cytomegalovirus upregulates nf-kb activity by transactivating the nf- κ b p105/p50 and p65 promoters. Journal of Virology 695391–5400
    [Google Scholar]
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