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(Gln22-Ser23) 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(Delta1-42), 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(Delta1-42) and p53(Gln22-Ser23) 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(Delta1-42) and p53(Gln22-Ser23). Taken together, these data suggest that within residues 43-63 lie an apoptotic domain as well as another transcriptional activation domain. We therefore postulate that the apoptotic activity in p53(Gln22-Ser23) and p53(Delta1-42) is still transcription-dependent.
Zhu
J
J
Program in Gene Regulation, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.
Zhou
W
W
Jiang
J
J
Chen
X
X
D017209:Apoptosis; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D016296:Mutagenesis; D017354:Point Mutation; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D016159:Tumor Suppressor Protein p53