Effects of p51/p63 missense mutations on transcriptional activities of p53 downstream gene promoters

Shunsuke Kato, Akira Shimada, Motonobu Osada, Shuntaro Ikawa, Masuo Obinata, Akira Nakagawara, Ryunosuke Kanamaru, Chikashi Ishioka

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The p51/p63 gene is a homologue of p53, the product of which acts as a transcriptional activator by binding to p53-responsive elements in the promoter regions of several p53 downstream genes. Recently, we identified four distinct mutations in the p51/p63 gene after screening >200 human tumors and cell lines. Because all of the detected p51/p63 mutations were missense mutations, the pathogenic effect of these mutations is difficult to determine without performing a functional analysis. In this study, we examined the transcriptional activity of tumor-derived p51/p63 missense mutations using a yeast-based assay and compared the data with that of artificial p51/p63 missense mutations at residues corresponding to the positions and substituted residues of p53 mutation 'hotspots.' Although most of the p51/p63 missense mutations at the p53 hotspot residues were unable to transactivate the promoters used in this study, the tumor-derived p51/p63 missense mutations retained their ability to transactivate the MDM2 and/or the BAX promoter but not the p21/WAF1 promoter. These results suggest that the p51/p63 mutation might be involved in an unknown tumor suppression pathway distinct from that of p53.

Original languageEnglish
Pages (from-to)5908-5911
Number of pages4
JournalCancer Research
Volume59
Issue number23
Publication statusPublished - Dec 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kato, S., Shimada, A., Osada, M., Ikawa, S., Obinata, M., Nakagawara, A., Kanamaru, R., & Ishioka, C. (1999). Effects of p51/p63 missense mutations on transcriptional activities of p53 downstream gene promoters. Cancer Research, 59(23), 5908-5911.