Identification of a novel p53 functional domain that is necessary for mediating apoptosis

The ability of p53 to induce apoptosis requires its sequence-specific DNA binding activity; however, the transactivation-deficient p53(Gln(22)-Ser(23)) can still induce apoptosis, Previously, we have shown that the region between residues 23 and 97 in p53 is necessary for such activity, In an effort to more precisely map a domain necessary for apoptosis within the N terminus, we found that deletion of the N-terminal 23 amino acids compromises, but does not abolish, p53 induction of apoptosis, Surprisingly, p53(Delta 1-42), which lacks the N-terminal 42 amino acids and the previously defined activation domain, retains the ability to induce apoptosis to an even higher level than wild-type p53, A more extensive deletion, which eliminates the N-terminal 63 amino acids, renders p53 completely inert in mediating apoptosis. In addition, we found that both p53(Delta 1-42) and p53(Gln(22)-Ser(23)) can activate a subset of cellular p53 targets. Furthermore, we showed that residues 53 and 54 are critical for the apoptotic and transcriptional activities of both p53(Delta 1-42) and p53(Gln(22)-Ser(23)). Taken together, these data suggest that within residues 43-63 lie an apoptotic domain as web as another transcriptional activation domain. We therefore postulate that the apoptotic activity in p53(Gln(22)-Ser(23)) and p53(Delta 1-42) is still transcription-dependent.