Lack of correlation between p53-dependent transcriptional activity and the ability to induce apostosis among 179 mutant p53s

Yuichi Kakudo, Hiroyuki Shibata, Kazunori Otsuka, Shunsuke Kato, Chikashi Ishioka

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Tumor suppressor p53-dependent apoptosis is thought to be one of the most important tumor-suppressive functions in human tumorigenesis. However, whether the major mechanism underlying the p53-dependent apoptosis is transactivation dependent or independent remains unclear. Using 179 mutant p53s with diverse transcriptional activities for distinct p53-binding sequences in yeast, we evaluated both their sequence-specific transcriptional activities on six p53 target genes and their ability to induce apoptosis in Saos-2 cells. These mutant p53s also represented diversity in their ability to both transactivate target genes and induce apoptosis. We identified 17 mutant p53s with superior ability to induce apoptosis than wild-type p53 that tend to cluster at residues 121 or 290 to 292. There was no significant correlation between the two functional properties on any single target gene examined. Furthermore, the 17 mutant p53s were not classified in a specific cluster by hierarchical cluster analysis on their diverse transcriptional activities, indicating that these mutant p53s were not similar in the transcriptional activity of downstream genes. These results suggested that transactivation-dependent; apoptosis does not always play a major role in p53-depenclent apoptosis, indirectly supporting the importance role of the transactivation-independent mechanism.

Original languageEnglish
Pages (from-to)2108-2114
Number of pages7
JournalCancer Research
Volume65
Issue number6
DOIs
Publication statusPublished - 2005 Mar 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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