Figure 1.

The two faces of p53. Activation of p53, such as by DNA damage, elicits either a protective response (Left) or an apoptotic response (Right). A third possible outcome associated with decreased cell survival is “G₁ checkout” (55), in which cells undergo an irreversible arrest. These possible outcomes appear to be determined largely by cell type and possibly also by the type of DNA damage incurred. The paper by Eller et al. (11) demonstrates that the protective “face” of p53 can be induced by treatment of cells with thymidine dinucleotide (pTpT), in the absence of DNA damage. Thus, functional inactivation of p53, such as by mutations occurring in cancer cells, can allow cells to escape p53-mediated apoptosis. At the same time, mutant p53 cells exhibit a condition of genomic instability, cell cycle checkpoint loss, and decreased ability to repair subsequent DNA damage.