Mechanism of p53-Dependent Apoptosis and its Role in Breast Cancer Therapy.
Abstract
The ability of pS3 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 22 and 97 in p53 is necessary for such activity. In an effort to more precisely map adomain 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 pS3 targets. Furthermore, we showed that residues 53 and 54 are critical for the apoptotic and transcriptional activities of both p53(Al- 42) and p53(gln22-ser23). Taken together, these data suggest that within residues 43 to 63 lies an apoptotic domain as well as another transcriptional activation domain. We therefore postulate that the apoptotic activity in p53(g1n22-ser23) and p53(Deltal-42) is still transcription-dependent.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA356207
Entities
People
- Xinbin Chen
Organizations
- Medical College of Georgia