The p53 tumor suppressor protein is accumulated in response to X-irradiation. This accumulation is due to inhibition of its ubiquitin-dependent proteasomal degradation, not by increasing its mRNA. Phosphorylation of p53 at Ser15, Thr18, and Ser20 is now generally believed to be a primal mechanism of p53 accumulation because these phosphorylation sites are located within a region responsible for the interaction between p53 and its specific ubiquitin ligase, MDM2. However, the physiological significance of these modifications remains elusive. We established cell lines expressing alanine mutant p53 at these sites. After 4-Gy X-irradiation, alanine mutant p53, as well as wild-type p53, were accumulated. This result indicates phosphorylation of p53 at Ser15, Thr18, and Ser20 may not be indispensable for X-ray-induced p53 accumulation. It is suggested that an unidentified mechanism, other than inhibiting p53-MDM2 interaction, may be involved in p53 accumulation after irradiation.
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