The short history of p53 contains an overwhelming number of facts and hypotheses, presenting the challenge of integrating diverse and sometimes mutually exclusive ideas into a coherent picture. It is important to make a distinction between p53 tumor suppressor activity, the mechanism of which remains speculative, and p53 responses to DNA damage, which are well characterized. Because critical steps in tumorigenesis involve genomic fixation of DNA damage-induced mutations, it seems reasonable to assume that DNA damage signaling to p53 would activate p53 tumor suppressor activity. However, this has not been demonstrated, and p53 tumor suppressor activity may not require the acute p53 response to DNA damage (Komarov et al., 1999). Nonetheless, the genotoxic chemicals and ionizing radiation that are clinically used to treat human cancer indisputably activate wild type p53.
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McLure, K.G., Kastan, M.B. (2007). 20 Years of DNA Damage Signaling to p53. In: Hainaut, P., Wiman, K.G. (eds) 25 Years of p53 Research. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-2922-6_3
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