The C-terminus of mutant p53 is necessary for its ability to interfere with growth arrest or apoptosis

The ability to suppress wild type p53-independent apoptosis may play an imp ortant role in the oncogenicity of p53 mutant proteins. However, structural elements necessary for this activity are unknown. Furthermore, it is uncle ar whether this mutant p53 mediated inhibition is specific to the apoptotic pathway or a more general suppression of the cellular response to stress. We observed that an unmodified C-terminus was required for the suppression of apoptosis by the p53 135(Ala to Val) oncogenic p53 mutant. It was also r equired for the novel activity of G(2) arrest suppression, the predominant response at low levels of genotoxic stress. These observations are consiste nt with a model whereby mutant p53 suppressive activity is not specific to the apoptotic pathway, but rather increases the threshold of genotoxic stre ss needed for a DNA damage response to occur. Furthermore, these observatio ns indicate that it may be possible to selectively kill mutant p53 expressi ng cells based on the lower sensitivity of their growth arrest response.