Abstract
INACTIVATION of the retinoblastoma susceptibility gene (RB-1) has been associated with the aetiology of many types of human cancers, leading to the classification of RB-1 as an anti-oncogene or tumour suppressor gene1–13. Given that the protein product of RB-1 (Rb) has a nuclear localization and DNA-binding activity in vitro, it is possible that Rb regulates transcription of certain genes. The promoter of the c-fos gene might be a target for regulation by Rb, because both v-fos and RB-1 are associated with the induction of osteosarcomas in mice and humans, respectively14,15. Also,fos expression is thought to be required for quiescent cells to enter the cell cycle, making the fos promoter an attractive target for suppressors of cell growth16–18. Here we report that Rb can repress c-fos expression and AP-1 transcriptional activity in both serum-induced and cycling 3T3 cells. We have mapped a cis-acting element in the human c-fos promoter that can confer repression by Rb to a heterologous promoter. We have the termed the cis-acting sequence regulated by Rb the retinoblastoma control element.
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References
Lee, W.-H. et al. Nature 329, 642–645 (1987).
Horowitz, J. M. et al. Science 243, 937–940 (1989).
Friend, S. H. et al. Nature 323, 643–646 (1986).
Horowitz, J. M. et al. Proc. natn. Acad. Sci U.S.A. (in the press).
Lee, E. Y.-H. P. et al. Science 241, 218–221 (1988).
T'Ang, A., Varley, J. M., Chakraborty, S. & Murphree, A. L. Science 242, 263–266 (1988).
Harbour, J. W. et al. Science 241, 353–357 (1988).
Yokota, J. et al. Oncogene 2, 471–475 (1988).
Horowitz, J. M., Park, S.-H., Yandell, D. W. & Weinberg, R. A. Curr. Comm. Molec. Biol: Recessive Oncogenes and Tumor Suppression, 101–107 (Cold Spring Harbor, New York 1989).
Shew, J.-Y., Ling, N., Yang, X., Fodstad, O. & Lee, W.-H. Oncogene Res. 1, 205–211 (1989).
Toguchida, J. et al. Cancer Res. 48, 3939–3943 (1988).
Weischselbaum, R., Beckett, M. & Diamond, A. Proc. natn. Acad. Sci. U.S.A. 85, 2106–2109 (1988).
Bookstein, R., Shew, J.-Y., Chen, P.-L., Scully, P. & Lee, W.-H. Science 247, 712–714 (1990).
Holt, J. T., Venkat Gopal, T., Moulton, A. D. & Nienhuia, A. W. Proc. natn. Acad. Sci. U.S.A. 83, 4794–4798 (1986).
Nishijura, K. & Murray, J. M. Molec. cell. Biol. 7, 639–649 (1987).
Riabowol, K. T., Vosatka, R. J., Ziff, E. B., Lamb, N. J. & Feramisco, J. R. Molec. cell. Biol. 8, 1670–1676 (1988).
Finkel, M. P., Biskis, B. O. & Jinkins, P. B. Science 151, 698–701 (1966).
Finkel, M. P., Reilly, C. A. & Biskis, B. O. Front. Radiat. Ther. Oncol. 10, 28–39 (1975).
Gilman, M. Z., Wilson, R. N. & Weinberg, R. A. Molec. cell. Biol. 6, 4305–4316 (1986).
Lee, W., Mitchell, P. & Tjian, R. Cell 49, 741–752 (1987).
Curran, T. & Franza, R. R. Cell 55, 395–397 (1988).
Bernards, R. et al. Proc. natn. Acad. Sci. U.S.A. 86, 6474–6478 (1989).
Baldwin, A. S. and Sharp, P. A. Proc. natn. Acad. Sci. U.S.A. 85, 723–727 (1988).
Whyte, P. et al. Nature 334, 124–129 (1988).
DeCaprio, J. A. et al. Cell 54, 275–283 (1988).
Dyson, N., Howley, P. M., Munger, K. & Harlow, E. Science 243, 934–937 (1989).
Landschultz, W. H., Johnson, P. F. & McKnight, S. L. Science 240, 1759–1763 (1988).
Treisman, R. Cell 46, 567–574 (1986).
Prywes, R. & Roeder, R. G. Cell 47, 777–784 (1986).
Frisch, T. M., Prywes, R. & Roeder, R. G. Molec. cell. Biol. 7, 3490–3502 (1987).
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Robbins, P., Horowitz, J. & Mulligan, R. Negative regulation of human c-fos expression by thes retinoblastoma gene product. Nature 346, 668–671 (1990). https://doi.org/10.1038/346668a0
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DOI: https://doi.org/10.1038/346668a0
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