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p14ARF links the tumour suppressors RB and p53

Abstract

Most human cancers show perturbation of growth regulation mediated by the tumour-suppressor proteins retinoblastoma (RB) and p53 (ref. 1), indicating that loss of both pathways is necessary for tumour development. Loss of RB function leads to abnormal proliferation related to the deregulation of the E2F transcription factors, but also results in the activation of p53, which suppresses cell growth. Here we show that E2F-1 directly activates expression of the human tumour-suppressor protein p14ARF (the mouse homologue is called p19ARF), which binds to the MDM2-p53 complex and prevents p53 degradation2,5. These results complete a pathway linking abnormal proliferative signals, such as loss of RB, with the activation of a p53 response, through E2F-1 and p14ARF. They suggest that E2F-1, a protein inherently activated by cell-cycle progression, is part of a fail-safe mechanism to protect against aberrant cell growth.

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Figure 1: E2F-1 induced p14ARF protein expression.

References

  1. Palmero, I. & Peters, G. Cancer Surv. 27, 351–367 (1996).

    Google Scholar 

  2. Pomerantz, J.et al. Cell 92, 713–723 (1998).

    Google Scholar 

  3. Zhang, Y., Xiong, Y. & Yarbrough, W. G. Cell 92, 725–734 (1998).

    Google Scholar 

  4. Stott, F. et al. EMBO J. (in the press).

  5. Kamijo, T.et al. Proc. Natl Acad. Sci. USA 95, 8292–8297 (1998).

    Google Scholar 

  6. Phillips, A. C., Bates, S., Ryan, K. M., Helin, K. & Vousden, K. H. Genes Dev. 11, 1853–1863 (1997).

    Google Scholar 

  7. Lukas, J., Petersen, B. O., Holm, K., Bartek, J. & Helin, K. Mol. Cell. Biol. 16, 1047–1057 (1996).

    Google Scholar 

  8. Kamijo, T.et al. Cell 91, 649–659 (1997).

    Google Scholar 

  9. Morgenbesser, S. D., Williams, B. O., Jacks, T. & DePinho, R. A. Nature 371, 72–74 (1994).

    Article  ADS  CAS  Google Scholar 

  10. Lowe, S. W. & Ruley, H. E. Genes Dev. 7, 535–545 (1993).

    Google Scholar 

  11. Hermeking, H. & Eick, D. Science 265, 2091–2092 (1994).

    Google Scholar 

  12. Kowalik, T. F., DeGregori, J., Leone, G., Jakoi, L. & Nevins, J. R. Cell Growth Differ. 9, 113–118 (1998).

    Google Scholar 

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Bates, S., Phillips, A., Clark, P. et al. p14ARF links the tumour suppressors RB and p53. Nature 395, 124–125 (1998). https://doi.org/10.1038/25867

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