1887

Abstract

The gene family encodes 2IK proteins that reside on the inner face of the plasma membrane and bind GTP and GDP with an equally high affinity. Cotransfection of NIH 3T3 cells with a mammalian expression vector containing a viral Harvey-raj (v-Ha-ras) cDNA, together with a plasmid (pCMVCAT) carrying the immediate early (IE) enhancer of the murine cytomegalovirus (MCMV) linked to the chloramphenicol acetyltrans- ferase (CAT) reporter gene strongly stimulated CAT activity. Basal levels of pCMVCAT expression as well as trans-activation by v- plasmid were both inhibited by cotransfection of an expression vector containing the dominant inhibitory mutant gene Ha-ras Asn-17. This indicates that the p21 protein is responsible for these activities. High pCMVCAT activation was also observed in cell lines carrying stably transfected oncogenes, activated by point mutation or amplification. To define the cis-acting DNA elements in the MCMV IE enhancer responsible for this trans-activation by p21 protein, we constructed several plasmids containing the CAT gene under control of MCMV IE enhancers that were deleted in different regions. The CAT assays demonstrated that several sequences were responsive to p21 protein. These sequences are scattered throughout the IE enhancer, upstream of the transcription start site, and contain responsive elements that are homologous to the binding sites for cellular transcription factors such as NFkB, API, ATF and SP1. Activation of the p2lprotein may thus be one of the signals that regulate IE genes transcription during MCMV infection.

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1994-07-01
2024-04-19
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References

  1. Arenzana-Seisdedos F., Israel N., Bachelerie F., Hazan U., Alcami J., Dautry F., Virelizier J.-L. 1989; c-Ha-ras transfection induces human immunodeficiency virus (HIV) tran-scription through the HIV enhancer in human fibroblasts and astrocytes. Oncogene 4:1359–1362
    [Google Scholar]
  2. Barbacid M. 1987; ras genes. Annual Review of Biochemistry 56:779–827
    [Google Scholar]
  3. Bishop J. M. 1985a; Viral oncogenes. Cell 42:23–38
    [Google Scholar]
  4. Bishop J. M. 1985b; Trends in oncogenes. Trends in Genetics 1:245–249
    [Google Scholar]
  5. Boldogh I., Abubakar S., Deng C. Z., Albrecht T. 1991a; Transcriptional activation of cellular oncogenes fos, jun, and myc by human cytomegalovirus. Journal of Virology 65:1568–1573
    [Google Scholar]
  6. Boldogh I., Abubakar S., Millinoff D., Deng C. Z., Albrecht T. 1991b; Cellular oncogene activation by human cytomegalovirus, lack of correlation with virus infectivity and immediate early gene expression. Archives of Virology 118:163–177
    [Google Scholar]
  7. Bortner D. M., Langer S. J., Ostrowski M. C. 1993; Nonnuclear oncogenes and the regulation of gene expression in transformed cells. Critical Reviews in Oncogenesis 4:137–160
    [Google Scholar]
  8. Cai H., Szeberenyi J., Cooper G. M. 1990; Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells. Molecular and Cellular Biology 10:5314–5323
    [Google Scholar]
  9. Chin K.-V., Ueda K., Pastan I., Gottesman M. M. 1992; Modulation of activity of the promoter of the human MDR1 gene by Ras and p53. Science 255:459–462
    [Google Scholar]
  10. Chirgwin J. M., Przybyla A. E., Macdonald R. J., Rutter W. J. 1979; Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299
    [Google Scholar]
  11. Dominguez I., Sanz L., Arenzana-Seisdedox F., Diaz-Meco M. T., Virelizier J.-L., Moscat J. 1993; Inhibition of protein kinase C ζ subspecies blocks the activation of an NF-kB-like activity in Xenopus laevis oocytes. Molecular and Cellular Biology 13:1290–1295
    [Google Scholar]
  12. Dorsch-Hasler K., Keil G. M., Weber F., Jasin M., Schaffner W., Koszinowski U. H. 1985; A long and complex enhancer activates transcription of the gene coding for the highly abundant immediate early mRNA in murine cytomegalovirus. Proceedings of the National Academy of Sciences, U.S.A 82:8325–8329
    [Google Scholar]
  13. Dotto G. P., Parada L. F., Weinberg R. A. 1985; Specific growth response of ras-transformed embryo fibroblasts to tumour promoters. Nature; London: 318472–475
    [Google Scholar]
  14. Downward J. 1992; Regulatory mechanisms for ras proteins. BioEssays 14:177–184
    [Google Scholar]
  15. Ebeling M., Keil G. M., Knust E., Koszinowski U. H. 1983; Molecular cloning and physical mapping of murine cytomegalovirus DNA. Journal of Virology 47:412–433
    [Google Scholar]
  16. Feig L. A., Cooper G. M. 1988; Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP. Molecular and Cellular Biology 8:3235–3243
    [Google Scholar]
  17. Galien R., Mercier G., Garcette M., Emanoil-Ravier R. 1991; RAS oncogene activates the intracisternalA particle long terminal repeat promoter through a c-AMP response element. Oncogene 6:849–855
    [Google Scholar]
  18. Gorman C. M., Moffat L. F., Howard B. H. 1982; Recombinant genomes which express chloramphenicol acetyl-transferase in mammalian cells. Molecular and Cellular Biology 2:1044–1051
    [Google Scholar]
  19. Gribaudo G., Ravaglia S., Caliendo A., Cavallo R., Gariglio M., Martinotti M. G., Landolfo S. 1993; Interferons inhibit the onset of murine cytomegalovirus immediate-early gene transcription. Virology in press
    [Google Scholar]
  20. Hall C., Jacob E., Ringold G., Lee F. 1983; Expression and regulation of Escherichia colt lacZ gene fusion in mammalian cells. Journal of Molecular and Applied Genetics 2:101–109
    [Google Scholar]
  21. Hudson J. B. 1979; The murine cytomegalovirus as a model for the study of viral pathogenesis and persistent infections. Archives of Virology 62:1–29
    [Google Scholar]
  22. Imler J. L., Schartz C., Wasylyk C., Chatton B., Wasylyk B. 1988; A Harvey-ras responsive transcription element is also responsive to a tumour-promoter and to serum. Nature; London: 332275–278
    [Google Scholar]
  23. Kedar P. S., Lowry D. R., Widen S. G., Wilson S. H. 1990; Transfected human b-polymerase promoter contains a ras-responsive element. Molecular and Cellular Biology 10:3852–3856
    [Google Scholar]
  24. Keil G. M., Ebeling-Keil A., Koszinowski U. H. 1987; Sequence and structural organization of murine cytomegalovirus immediate-early gene 1. Journal of Virology 61:1901–1908
    [Google Scholar]
  25. Koszinowski U. H., Del Val M., Reddehase M. J. 1990; Cellular and molecular basis of the protective immune response to cytomegalovirus infection. Current Topics in Microbiology and Immunology 154:189–220
    [Google Scholar]
  26. Mcdougall J. K. 1990 Cytomegaloviruses Berlin: Springer-Verlag;
    [Google Scholar]
  27. Manning W. C., Mocarski E. S. 1988; Insertional mutagenesis of the murine cytomegalovirus genome: one prominant gene (ie2) is dispensable for growth. Virology 167:477–484
    [Google Scholar]
  28. Marx J. 1993; Forging a path to the nucleus. Science 260:1588–1590
    [Google Scholar]
  29. Medema R. H., Wubbolts R., Bos J. L. 1991; Two dominant inhibitory mutants of p21ras interfere with insulin-induced gene expression. Molecular and Cellular Biology 11:5963–5967
    [Google Scholar]
  30. Mercer J. A., Marks J. R., Spector D. H. 1983; Molecular cloning and restriction endonuclease mapping of the murine cytomegalovirus genome (Smith strain). Virology 129:94–106
    [Google Scholar]
  31. Messerle M., Buhler B., Keil G. M., Koszinowski U. H. 1992; Structural organization, expression, and functional characterization of the murine cytomegalovirus immediate-early gene 3. Journal of Virology 66:27–36
    [Google Scholar]
  32. Mocarski E. S. 1991; Initial events involved in cytomegalovirus-cell interactions. Transplantation Proceedings 23:43–47
    [Google Scholar]
  33. Moch H., Lang D., Stamminger T. 1992; Strong trans activation of the human cytomegalovirus major immediate-early enhancer by p40tax of human T cell leukemia virus type I via two repetitive tax-responsive sequence elements. Journal of Virology 66:7346–7354
    [Google Scholar]
  34. Oku N., Kaibuchi K., Fukumoto Y., Hori Y., Fujioka H., Takai Y. 1990; Comparison of the mode of action of ras p21 with those of protein kinases A and C in the stimulation of gene expression in NIH/3T3 cells. FEBS Letters 269:148–156
    [Google Scholar]
  35. Owen R., Ostrowski M. C. 1987; Rapid and selective alterations in the expression of cellular genes accompany conditional transcription of Ha-v-ra.v in NIH 3T3 cells. Molecular and Cellular Biology 7:2512–2520
    [Google Scholar]
  36. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  37. Sambucetti L. C., Cherrington J. M., Wilkinson G. W. G., Mocarski E. S. 1989; NF-kB activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EM BO Journal 8:4251–4258
    [Google Scholar]
  38. Satake M., Tamotsu I., Ito I. 1988; Modulation of polyomavirus enhancer binding proteins by Ha -ras oncogene. Oncogene 3:69–78
    [Google Scholar]
  39. Shelbourn S. L., Sissons J. G. P., Sinclair J. H. 1989; Expression of oncogenic ras in human teratocarcinoma cells induces partial differentiation and permissiveness for human cytomegalovirus infection. Journal of General Virology 70:367–374
    [Google Scholar]
  40. Varmus H. E. 1984; The molecular genetics of cellular oncogenes. Annual Review of Genetics 18:553–612
    [Google Scholar]
  41. Wasylyk C., Imler J. L., Perez-Mutul J., Wasylyk B. 1987; The c-Ha-ras oncogene and a tumor promoter activate the polyoma virus enhancer. Cell 48:525–534
    [Google Scholar]
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