Abstract
p53 protein is a key regulatory component of a stress-inducible cell-cycle checkpoint pathway in mammalian cells, which can promote either cell-growth arrest or apoptosis, depending on the type of cell and damaging agent utilized. Environmental insults that can activate the p53 pathway are quite distinct, and include ionizing and nonionizing radiation (1–5), antimetabolites which inhibit ribonucleotide biosynthesis (6), inhibitors of spindle formation (7), microtubule-affecting drugs (8), factors inducing differentiation (9), signaling pathways activated in transformed cells during anchorage-independent growth (10), heat shock (11), and hypoxia (12).
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References
Hall., P. A., McKee, P. H., Menage, H., Dover, R., and Lane, D. P. (1993) High levels of p53 protein in UV irradiated human skin. Oncogene 8, 203–207.
Campbell, C., Quinn, A. G., Angus, B., Farr, P. M., and Rees, J. (1993) Wavelength specific patterns of p53 induction in human skin following exposure to UV radiation. Cancer Res. 53, 2697–2699.
Merritt, A. J., Potten, C. S., Kemp, C. J., Hickman, J. A., Balmain, A., Lane, D. P., et al. (1994) The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Res. 54, 614–617.
Midgley, C. M., Owens, B., Briscoe, C. V., Thomas, D. B., Lane, D. P., and Hall, P. A. (1995) Coupling between gamma irradiation, p53 induction, and the apoptotic response depends upon cell type in vivo. J. Cell. Sci. 108, 1843–1848.
MacCallum, D. E., Hupp, T. R., Midgley, C. A., Stuart, D., Campbell, S. J., Harper, A., et al. (1996) The p53 response to ionising radiation in adult and developing murine tissues. Oncogene 13, 2575–2587.
Linke, S. P., Clarkin, K. C., DiLeonardo, A., Tsou, A., and Wahl, G. M. (1996) A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev. 10, 934–947.
Cross, S. M., Sanchez, C. A., Morgan, C. A. Schimke, M. K., Ramel, S., Idzerda, R. L., et al. (1995) A p53-dependent mouse spindle checkpoint. Science 267, 1353–1356.
Tishler, R. B., Lamppu, D. M., Park, S., and Price, B. D. (1995) Microtubuleactive drugs taxol, vinblastine, and nocodazole increase the levels of transcriptionally active p53. Cancer Res. 55, 6021–6025.
Lutzker, S. G. and Levine. A. J. (1996) A functionally inactive p53 protein in teratocarcinoma cells is activated by either DNA damage or cellular differentiation. Nature Med. 2, 804–810.
Nikiforov, M. A., Hagen, K., Ossovskaya, V. S., Connor, T. M. F., Lowe, S. W., Deichman, G. I., et al. (1996) p53 modulation of anchorage independent growth and experimental metastasis. Oncogene 13, 1709–1719.
Sugano, T., Nitta, M., Ohmori, H., and Yamaizumi, M. (1995) Nuclear accumulation of p53 in normal human fibroblasts is induced by various cellular stresses which evoke the heat shock response, independently of the cell cycle. Jpn. J. Cancer Res. 86, 415–418.
Graeber, T. G., Osmanian, C., Jacks, T., Housman, D. E., Koch, C. J., Lowe, S. W. et al. (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379, 88–91.
Kastan, M. B., Onyekwere, O., Sidransky, D., Vogelstein, B., and Craig, R. W. (1991). Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51, 6304–6311.
Lu, X. and Lane, D. P. (1993). Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell 75, 765–778.
Hupp T. R. and Lane, D. P. (1995) Two distinct signalling pathways activate the latent DNA binding function of p53 in a casein kinase II-independent manner. J. Biol. Chem. 270, 18,165–18,174.
Hupp, T. R., Sparks, A., and Lane, D. P. (1995) Small peptides activate the latent DNA binding function of p53. Cell 83, 237–245.
Hupp, T. R. and Lane D. P. (1994) Regulation of the cryptic sequence-specific DNA binding function of p53 by protein kinases. Cold Spring Harbor Symp. Quant. Biol. 59, 195–206.
El-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., and Vogelstein, B. (1992) Definition of a consensus binding site for p53. Nature Genet. 1, 45–49.
Hupp, T. R., Meek, D. W., Midgley, C. A., and Lane, D. P. (1992) Regulation of the specific DNA binding function of p53. Cell 71, 875–886.
Shaulsky, G., Ben-Ze’ev, A., and Rotter, V. (1990) Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells. Oncogene 5, 1707–1711.
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Blaydes, J.P., Sparks, A., Hupp, T.R. (1999). Activation of p53 Protein Function in Response to Cellular Irradiation. In: Henderson, D.S. (eds) DNA Repair Protocols. Methods in Molecular Biology™, vol 113. Humana Press. https://doi.org/10.1385/1-59259-675-4:591
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DOI: https://doi.org/10.1385/1-59259-675-4:591
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