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Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53

Nature volume 363, pages 281–283 (1993)Cite this article

Abstract

THE p53 protein is apparently central to the development of human cancers because both alleles are often found to be mutated in different tumour types1. In addition, wild-type p53 can inhibit transformation by viral and cellular oncogenes in vitro, so p53 has been classified as a tumour suppressor2. Investigations of the normal function of p53 have indicated that at least one of its functions could involve the activation of gene expression through the binding of specific DNA-regulatory sequences3,4. Also, overexpression of p53 can mediate growth arrest5 and repress transcription from a variety of promoters6,7. We demonstrate here both in vivo and in vitro that expression of wild-type p53 specifically represses the activity of promoters whose initiation is dependent on the presence of a TAT A box. Promoters whose accurate transcription is directed by a pyrimidine-rich initiator element, however, are immune to the effects of p53. Furthermore, we observe that repression is mediated by an interaction of p53 with basal transcription factor(s). Thus, p53 appears to repress the activity of certain promoters through direct communication with TATA box-dependent basal transcription machinery.

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References

  1. Hollstein, M., Sidransky, D., Vogelstein, B. & Harris, C. C. Science 253, 49–53 (1991).

    Article  ADS  CAS  Google Scholar 

  2. Finlay, C. A., Hinds, P. W. & Levine, A. J. Cell 57, 1083–1093 (1989).

    Article  CAS  Google Scholar 

  3. Zambetti, G. P., Bargonetti, J., Walker, K., Prives, C. & Levine, A. J. Genes Dev. 6, 1143–1152 (1992).

    Article  CAS  Google Scholar 

  4. Farmer, G. et al. Nature 358, 83–86 (1992).

    Article  ADS  CAS  Google Scholar 

  5. Baker, S. J., Markowitz, K., Fearon, E. R., Willson, J. K. V. & Vogelstein, B. Science 249, 912–915 (1990).

    Article  ADS  CAS  Google Scholar 

  6. Ginsberg, D., Mechta, F., Yaniv, M. & Oren, M. Proc. natn. Acad. Sci. U.S.A. 88, 9979–9983 (1991).

    Article  ADS  CAS  Google Scholar 

  7. Lechner, M. S. et al. EMBO J. 11, 3045–3052 (1992).

    Article  CAS  Google Scholar 

  8. Chin, K.-V., Ueda, K., Pastan, I. & Gottesman, M. M. Science 255, 459–462 (1992).

    Article  ADS  CAS  Google Scholar 

  9. O'Shea-Greenfield, A. & Smale, S. T. J. biol. Chem. 267, 1391–1402 (1992).

    CAS  Google Scholar 

  10. Ptashne, M. Science 335, 683–698 (1988).

    CAS  Google Scholar 

  11. Pugh, B. F. & Tjian, R. Genes Dev. 5, 1935–1945 (1991).

    Article  CAS  Google Scholar 

  12. Pugh, B. F. & Tjian, R. Cell 61, 1187–1197 (1990).

    Article  CAS  Google Scholar 

  13. Inostroza, J. A., Mermelstein, F. H., Ha, I., Lane, W. S. & Reinberg, D. Cell 70, 477–489 (1992).

    Article  CAS  Google Scholar 

  14. Meisterernst, M. & Roeder, R. G. Cell 67, 557–567 (1991).

    Article  CAS  Google Scholar 

  15. Meisterernst, M., Roy, A. L., Lieu, H. M. & Roeder, R. G. Cell 66, 981–993 (1991).

    Article  CAS  Google Scholar 

  16. Seto, E. et al. Proc. natn. Acad Sci. U.S.A. 89, 12028–12032 (1992).

    Article  ADS  CAS  Google Scholar 

  17. Parvin, J. D., Timmers, H. T. M. & Sharp, P. A. Cell 68, 1135–1144 (1992).

    Article  CAS  Google Scholar 

  18. Maltzman, W. & Czyzyk, L. Molec. cell. Biol. 4, 1689–1694 (1984).

    Article  CAS  Google Scholar 

  19. Kastan, M. B., Onyekwere, O., Sidransky, D., Vogelstein, B. & Craig, R. W. Cancer Res. 51, 6304–6311 (1991).

    CAS  Google Scholar 

  20. Martinez, J., Georgoff, I., Martinez, J. & Levine, A. J. Genes Dev. 5, 151–159 (1991).

    Article  CAS  Google Scholar 

  21. Nichols, A. F. & Sancar, A. Nucleic Acids Res. 20, 2441–2446 (1992).

    Article  CAS  Google Scholar 

  22. Scheffner, M., Münger, K., Byrne, J. C. & Howley, P. M. Proc. natn. Acad. Sci. U.S.A. 88, 5523–5527 (1991).

    Article  ADS  CAS  Google Scholar 

  23. Morris, G. F. & Mathews, M. B. J. Virol. 65, 6397–6406 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Gorman, C. in DNA Cloning (ed., Glover, D. M.) Vol. II, 143–159 (IRL. Oxford, 1985).

    Google Scholar 

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

    Article  CAS  Google Scholar 

  26. Westin, G., Gerster, T., Müller, M. M., Schaffner, G. & Schaffner, G. & Schaffner, W. Nucleic Acids Res. 15, 6787–6798 (1987).

    Article  CAS  Google Scholar 

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Author notes

  1. David H. Mack

    Present address: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, 94305, USA

  2. Laimonis A.Laimins: To whom correspondence should be addressed

Authors and Affiliations

  1. Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Avenue, MC1028, Chicago, Illinois, 60637, USA

    David H. Mack & Laimonis A. Laimins

  2. Howard Hughes Medical Institute, The University of Chicago, 5841 S. Maryland Avenue, MC1028, Chicago, Illinois, 60637, USA

    Laimonis A. Laimins

  3. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA

    Jai Vartikar & James M. Pipas

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  1. David H. Mack
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  2. Jai Vartikar
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  3. James M. Pipas
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  4. Laimonis A. Laimins
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Mack, D., Vartikar, J., Pipas, J. et al. Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53. Nature 363, 281–283 (1993). https://doi.org/10.1038/363281a0

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