Abstract
NORMALLY growing cells promptly cease DNA synthesis when exposed to genotoxic stresses, such as radiation, and this cell-cycle arrest prevents the accumulation of mutations1,2. The transcription factor interferon regulatory factor (IRF)-1 is essential for the regulation of the interferon system3–5, inhibits cell growth, and manifests tumour-suppressor activities6,7. Here we show that mouse embryonic fibroblasts (EFs) lacking IRF-1 are deficient in their ability to undergo DNA-damage-induced cell-cycle arrest. A similar phenotype has been observed in EFs lacking the tumour suppressor p53 (refs 8, 9), although the expression of IRF-1 and p53 are independent of one another. Furthermore, we show that transcriptional induction of the gene encoding p21 (WAF1, CIP1)10–12 a cell-cycle inhibitor, by γ-irradiation is dependent on both p53 and IRF-1, and that the p21 promoter is activated, either directly or indirectly, by both in a transient cotransfection assay. These two tumour-suppressor transcription factors therefore converge functionally to regulate the cell cycle through the activation of a common target genes.
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References
Hartwell, L. Cell 71, 543–546 (1992).
Hunter, T. & Pines, J. Cell 79, 573–582 (1994).
Matsuyama, T. et al. Cell 75, 83–97 (1993).
Kamijo, R. et al. Science 263, 1612–1615 (1994).
Kimura, T. et al. Science 264, 1921–1924 (1994).
Tanaka, N. et al. Cell 77, 829–839 (1994).
Tamura, T. et al. Nature 376, 596–599 (1995).
Vogelstein, B. & Kinzler, K. W. Cell 70, 523–526 (1992).
Liebermann, D. A., Hoffman, B. & Steinman, R. A. Oncogene 11, 199–210 (1995).
El-Deiry, W. S. et al. Cell 75, 817–825 (1993).
Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K. & Elledge, S. J. Cell 75, 805–816 (1993).
Xiong, Y. et al. Nature 366, 701–704 (1993).
Lowe, S. W., Ruley, H. E., Jacks, T. & Housman, D. E. Cell 74, 957–967 (1993).
Sherr, C. J. & Roberts, J. M. Genes Dev. 9, 1149–1163 (1995).
Brugarolas, J. et al. Nature 377, 552–557 (1995).
Darnell Jr, J. E., Kerr, I. M. & Stark, G. R. Science 264, 1415–1421 (1994).
Chin, Y. E. et al. Science 272, 719–722 (1996).
Meraz, M. A. et al. Cell 84, 431–442 (1996).
Durbin, J. E., Hackenmiller, R., Simon, M. C. & Levy, D. E. Cell 84, 443–450 (1996).
Kastan, M. B., Onyekwere, O., Sidransky, D., Vogelstein, B. & Craig, R. W. Cancer Res. 51, 6304–6311 (1991).
El-Deiry, W. S. et al. Cancer Res. 54, 1169–1174 (1994).
El-Deiry, W. S. et al. Cancer Res. 55, 2910–2919 (1995).
Parker, S. B. et al. Science 267, 1024–1027 (1995).
Halevy, O. et al. Science 267, 1018–1021 (1995).
Cross, S. M. et al. Science 267, 1353–1356 (1995).
Willman, C. L. et al. Science 259, 968–971 (1993).
Matsushime, H. et al. Molec. Cell Biol. 14, 2066–2076 (1994).
Harada, H. et al. Science 259, 971–974 (1993).
Baker, S. J., Markowitz, S., Fearon, E. R., Willson, J. K. V. & Vogelstein, B. Science 249, 912–915 (1990).
Haupt, Y., Rowan, S., Shaulian, E., Vousden, K. H. & Oren, M. Genes Dev. 9, 2170–2183 (1995).
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Tanaka, N., Ishihara, M., Lamphier, M. et al. Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage. Nature 382, 816–818 (1996). https://doi.org/10.1038/382816a0
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DOI: https://doi.org/10.1038/382816a0
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