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Phorbol ester induces the transcriptional stimulatory activity of the SV40 enhancer

Abstract

Phorbol ester tumour promoters can induce the transcription of a number of genes1, including c-myc and c-fos2. These genes are part of a group referred to as ‘competence’ genes3,4 because they are expressed very early after quiescent cells are stimulated to enter the cell cycle5–7. The ‘competence’ genes are coordinately induced by serum and by factors such as platelet-derived growth factor and fibroblast growth factor1,2,8–12. These factors, as well as the tumour promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), are thought to exert their action by a mechanism involving the activation of protein kinase C13–16. It is likely that these factors induce the transcription of the ‘competence’ genes either by activating specific transcription factors or by increasing their intracellular concentration; either mechanism may be mediated by protein kinase C. One approach to identifying such a putative transcription factor is to characterize the cis-acting transcriptional control elements that serve as a target site for the factor. Here we report that, in a human hepatoma cell line, TPA can specifically induce the activity of the simian virus 40 (SV40) transcriptional enhancer element. Since the SV40 enhancer is a thoroughly characterized cis-actitng element17–19, this system may facilitate the eventual identification of the trans-acting factor(s) whose activity is modified by TPA treatment.

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References

  1. Lau, L. F. & Nathans, D. EMBO J. 4, 3145–3151 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Greenberg, M. E. & Ziff, E. B. Nature 311, 433–438 (1984).

    ADS  CAS  PubMed  Google Scholar 

  3. Cochran, B. H., Zullo, J., Verma, I. & Stiles, C. D. Science 226, 1080–1082 (1984).

    ADS  CAS  PubMed  Google Scholar 

  4. Cochran, B. H., Reffel, A. C. & Stiles, C. D. Cell 33, 939–947 (1983).

    CAS  PubMed  Google Scholar 

  5. Callahan, M., Cochran, B. H. & Stiles, C. D. in Growth Factors in Biology and Medicine (eds Evered, D., Nugent, J. & Whelan, J.) 87–97 (Pitman, London, 1985).

    Google Scholar 

  6. Scher, C. D., Shepard, R. C., Antoniades, H. N. & Stiles, C. D. Biochim. biophys. Acta 560, 217–241 (1979).

    CAS  PubMed  Google Scholar 

  7. Pledger, W. J., Stiles, C. D., Antoniades, H. N. & Scher, C. D. Proc. natn. Acad. Sci. U.S.A. 74, 4481–4485 (1977).

    ADS  CAS  Google Scholar 

  8. Persson, H., Gray, H. E. & Godeau, F. Molec. cell. Biol. 5, 2903–2912 (1985).

    CAS  PubMed  Google Scholar 

  9. Muller, R., Bravo, R., Burckhardt, J. & Curran, T. Nature 312, 716–720 (1984).

    ADS  CAS  PubMed  Google Scholar 

  10. Kruijer, W., Cooper, J. A., Hunter, T. & Verma, I. M. Nature 312, 711–716 (1984).

    ADS  CAS  PubMed  Google Scholar 

  11. Kelly, K., Cochran, B. H., Stiles, C. D. & Leder, P. Cell 35, 603–610 (1983).

    CAS  PubMed  Google Scholar 

  12. Stiles, C. D. Cell 33, 653–655 (1983).

    CAS  PubMed  Google Scholar 

  13. Brown, K. D. et al. Biochem. biophys. Res. Commun. 123, 377–384 (1984).

    CAS  PubMed  Google Scholar 

  14. Nishizuka, Y. Nature 308, 693–698 (1984).

    ADS  CAS  PubMed  Google Scholar 

  15. Berridge, M. J. Biochem. J. 220, 345–360 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Habnicht, A. J. R. et al. J. biol. Chem. 256, 12329–12335 (1981).

    Google Scholar 

  17. Zenke, M. et al. EMBO J. 5, 387–397 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Khoury, G. & Gruss, P. Cell 33, 313–314 (1983).

    CAS  PubMed  Google Scholar 

  19. Herr, W. & Clarke, G. Cell 45, 461–470 (1986).

    CAS  PubMed  Google Scholar 

  20. Scholer, H. et al. Science 232, 76–80 (1986).

    ADS  CAS  PubMed  Google Scholar 

  21. Gorman, C. M., Moffat, L. F. & Howard, B. H. Molec. cell. Biol. 2, 1044–1051 (1982).

    CAS  PubMed  Google Scholar 

  22. Graham, F. L. & van der Eb, A. J. Virology 52, 456–467 (1973).

    CAS  PubMed  Google Scholar 

  23. Castanaga, M. et al. J. biol. Chem. 257, 7847–7851 (1982).

    Google Scholar 

  24. Chandler, V. L., Maler, B. A. & Yamamoto, K. R. Cell 33, 489–499 (1983).

    CAS  PubMed  Google Scholar 

  25. Ponta, H. et al. Proc. natn. Acad. Sci. U.S.A. 82, 1020–1024 (1985).

    ADS  CAS  Google Scholar 

  26. Karin, M. et al. Cell 36, 371–379 (1984).

    CAS  PubMed  Google Scholar 

  27. Karin, M. et al. Molec. cell. Biol. (submitted).

  28. Serfling, E., Lubbe, A., Dorach-Hasler, K. & Schaffner, W. EMBO J. 4, 3851–3859 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Ryals, J., Dierks, P., Ragg, H. & Weissmann, C. Cell 41, 497–507 (1985).

    CAS  PubMed  Google Scholar 

  30. Goodbourn, S., Zinn, K. & Maniatis, T. Cell 41, 509–520 (1985).

    CAS  PubMed  Google Scholar 

  31. Fujita, T., Ohno, S., Yasumitsu, H. & Taniguchi, T. Cell 41, 489–496 (1985).

    CAS  PubMed  Google Scholar 

  32. Haslinger, A. & Karin, M. Proc. natn. Acad. Sci. U.S.A. 82, 8572–8576 (1985).

    ADS  CAS  Google Scholar 

  33. McKnight, S. Nucleic Acids Res. 8, 5949–5964 (1979).

    Google Scholar 

  34. Treisman, R. Cell 42, 889–902 (1985).

    CAS  PubMed  Google Scholar 

  35. Wildeman, A. G. et al., Molec. cell. Biol. 6, 2098–2105 (1986).

    CAS  PubMed  Google Scholar 

  36. Zur-Hausen, H., Yamamoto, N. & Bauer, G. Carcinogenesis 7, 617–623 (1982).

    CAS  Google Scholar 

  37. Zur-Hausen, H., O'Neill, F. J., Freese, U. K. & Hecker, E. Nature 272, 373–375 (1978).

    ADS  CAS  PubMed  Google Scholar 

  38. Eliasson, L., Nilsson, M. T., Kallin, B. & Klein, G. in Cellular Interactions by Environmental Tumor Promoters (eds Fujiki, H. et al.) 139–145 (Japan Sci. Soc. Press, Tokyo, 1984).

    Google Scholar 

  39. Fisher, P. B., Weinstein, I. B. & Ginsberg, H. S. Proc. natn. Acad. Sci. U.S.A. 75, 2311–2314 (1978).

    ADS  CAS  Google Scholar 

  40. Monier, R., Daya-Grosjean, L. & Sarasin, A. in Carcinogensis: Fundamental Mechanisms and Environmental Effects (eds Pullman, B., Tso, P. & Gelboin, H.) 371–378 (Reidel, Dordrecht, 1980).

    Google Scholar 

  41. Amtmann, E. & Sauer, G. Nature 296, 675–677 (1982).

    ADS  CAS  PubMed  Google Scholar 

  42. Heguy, A., West, A., Richards, R. I. & Karin, M. Molec. cell. Biol. 6, 2149–2157 (1986).

    CAS  PubMed  Google Scholar 

  43. Resendez, E. Jr et al. Molec. cell. Biol. 5, 1212–1219 (1985).

    CAS  PubMed  Google Scholar 

  44. Ott, M. O. et al. EMBO J. 3, 2505–2510 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Gorman, C. et al. Proc. natn. Acad. Sci. U.S.A. 79, 6777–6781 (1982).

    ADS  CAS  Google Scholar 

  46. Laimins, L. et al. Proc. natn. Acad. Sci. U.S.A. 79, 6453–6457 (1982).

    ADS  CAS  Google Scholar 

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Imbra, R., Karin, M. Phorbol ester induces the transcriptional stimulatory activity of the SV40 enhancer. Nature 323, 555–558 (1986). https://doi.org/10.1038/323555a0

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