title: A mutant P53 can activate apoptosis through a mechanism distinct from those induced by wild type P53.
abstract: A common mutation in P53 protein occurs at amino acid residue 281 in the DNA binding domain (P53(gly(281))), which results in loss of transcriptional regulation of P53 target genes and has been reported to gain pro-oncogenic functions. In the present study, we investigated the activity of P53(gly(281)) in P53-null PC3 human prostate cancer cells and found that the P53(gly(281)) induced apoptosis as efficiently as the wild-type P53 (wtP53). However, in contrast to wtP53-induced apoptosis, the P53(gly(281))-induced apoptosis was insensitive to overexpression of bcl-2. Thus, our findings indicate that while a mutation in the DNA binding domain of p53 may result in a more oncogenic form of the protein, it may also paradoxically result in the 'gain' of a new, alternative pathway for apoptosis.
authors.affiliation: The Prostate Centre at Vancouver General Hospital, Vancouver, BC, Canada
authors.forename: Ming
authors.initials: M
authors.lastname: He
authors.forename: Paul S
authors.initials: PS
authors.lastname: Rennie
authors.forename: Visia
authors.initials: V
authors.lastname: Dragowska
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Nelson
authors.forename: William
authors.initials: W
authors.lastname: Jia
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor