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

研究成果: Article査読

19 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)5908-5911
ページ数4
ジャーナルCancer Research
59
23
出版ステータスPublished - 1999 12 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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