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Induction of the growth inhibitor IGF-binding protein 3 by p53

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Abstract

TRANSCRIPTIONAL activation of target genes represents an important component of the tumour-suppressor function of p53 and provides a functional link between p53 and various growth-regulatory processes, including cell cycle progression (p21/WAF1)1á¤-3, DNA repair (GADD45)4 and apoptosis (bax)5. Here we use a differential cloning approach to identify the gene encoding insulin-like growth factor binding protein 3 (IGF-BP3) as a novel p53-regulated target gene. Induction of IGF-BP3 gene expression by wild-type but not mutant p53 is associated with enhanced secretion of an active form of IGF-BP3 capable of inhibiting mitogenic signalling by the insulin-like growth factor IGF-1. Our results indicate that IGF-BP3 may link p53 to potential novel autocrine/paracrine signalling pathways and to processes regulated by or dependent on IGF(s), such as cellular growth, transformation and survival.

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References

  1. El-Deiry, W. S. et al. Cell 75, 817–825 (1993).

    Article  CAS  Google Scholar 

  2. Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K. & Elledge, S. J. Cell 75, 805–816 (1993).

    Article  CAS  Google Scholar 

  3. Xiong, Y. et al. Nature 366, 701–704 (1993).

    Article  ADS  CAS  Google Scholar 

  4. Smith, M. L. et al. Science 266, 1376–1380 (1994).

    Article  ADS  CAS  Google Scholar 

  5. Miyashita, T. et al. Oncogene 9, 1799–1805 (1994).

    CAS  PubMed  Google Scholar 

  6. Shaw, P. et al. Proc. natn. Acad. Sci. U.S.A. 89, 4495–4499 (1992).

    Article  ADS  CAS  Google Scholar 

  7. Buckbinder, L., Talbott, R., Seizinger, B. R. & Kley, N. Proc. natn. Acad. Sci. U.S.A. 91, 10640–10644 (1994).

    Article  ADS  CAS  Google Scholar 

  8. Cubbage, M. L., Suwanichkul, A. & Powell, D. R. J. biol. Chem. 265, 12642–12649 (1990).

    CAS  PubMed  Google Scholar 

  9. El-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W. & Vogelstein, B. Nature Genet. 1, 45–49 (1992).

    Article  CAS  Google Scholar 

  10. Takenaka, I., Morin, F., Seizinger, B. R. & Kley, N. J. biol. Chem. 270, 5405–5411 (1995).

    Article  CAS  Google Scholar 

  11. Valentinis, B., Bhala, A., DeAngelis, T., Baserga, R. & Cohen, P. Molec. Endocr. 9, 361–367 (1995).

    CAS  PubMed  Google Scholar 

  12. Jones, J. I. & Clemmons, D. R. Endocr. Rev. 16, 3–34 (1995).

    CAS  PubMed  Google Scholar 

  13. Shimasaki, S. & Ling, N. Progr. Growth Factor Res. 3, 243–266 (1992).

    Article  Google Scholar 

  14. Baserga, R. Cell 79, 927–930 (1994).

    Article  CAS  Google Scholar 

  15. Resnicoff, M. et al. Cancer Res. 55, 2463–2469 (1995).

    CAS  PubMed  Google Scholar 

  16. Grigoriev, V. G., Moerman, E. J. & Goldstein, S. J. J. Cell Physiol. 160, 203–211 (1994).

    Article  CAS  Google Scholar 

  17. Swisshelm, K., Ryan, K., Tsuchiva, K. & Sager, R. Proc. natn. Acad. Sci. U.S.A. 92, 4472–4476 (1995).

    Article  ADS  CAS  Google Scholar 

  18. Cohen, P., Peehl, D. M., Graves, H. C. B. & Rosenfeld, R. G. J. Endocr. 142, 407–415 (1994).

    Article  CAS  Google Scholar 

  19. Yu, H. et al. Cancer Res. 55, 1603–1606 (1995).

    CAS  PubMed  Google Scholar 

  20. Yu, H. et al. Cancer Res. 55, 2104–2110 (1995).

    CAS  PubMed  Google Scholar 

  21. Harvey, M. et al. Oncogene 8, 2457–2467 (1993).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Genetics, Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, New Jersey, 08543-4000, USA

    Leonard Buckbinder, Randy Talbott, Susana Velasco-Miguel, Ivone Takenaka, Barbara Faha, Bernd R. Seizinger & Nikolai Kley

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  1. Leonard Buckbinder
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  2. Randy Talbott
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  3. Susana Velasco-Miguel
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  4. Ivone Takenaka
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  5. Barbara Faha
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  6. Bernd R. Seizinger
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  7. Nikolai Kley
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Buckbinder, L., Talbott, R., Velasco-Miguel, S. et al. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature 377, 646–649 (1995). https://doi.org/10.1038/377646a0

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  • DOI: https://doi.org/10.1038/377646a0

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