Identification of a Novel p53 Functional Domain That Is Necessary for Mediating Apoptosis

• Published in: The Journal of biological chemistry 1998-05, Vol.273 (21), p.13030-13036
• Main Authors: Zhu, Jianhui, Zhou, Wenjing, Jiang, Jieyuan, Chen, Xinbin
• Format: Article
• Language: English
• Subjects: Apoptosis; Base Sequence; Cell Line; DNA Primers; Mutagenesis; Point Mutation; Transcription, Genetic; Tumor Suppressor Protein p53 - chemistry; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.21.13030

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(Δ1–42), 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(Δ1–42) 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(Δ1–42) 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(Δ1–42) is still transcription-dependent.