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

Fingerprint

p53 Genes
Missense Mutation
Mutation
Neoplasms
Tumor Cell Line
Genetic Promoter Regions
Genes
Yeasts

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

Effects of p51/p63 missense mutations on transcriptional activities of p53 downstream gene promoters. / Kato, Shunsuke; Shimada, Akira; Osada, Motonobu; Ikawa, Shuntaro; Obinata, Masuo; Nakagawara, Akira; Kanamaru, Ryunosuke; Ishioka, Chikashi.

In: Cancer Research, Vol. 59, No. 23, 01.12.1999, p. 5908-5911.

Research output: Contribution to journalArticle

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, vol. 59, no. 23, pp. 5908-5911.
Kato S, Shimada A, Osada M, Ikawa S, Obinata M, Nakagawara A et al. Effects of p51/p63 missense mutations on transcriptional activities of p53 downstream gene promoters. Cancer Research. 1999 Dec 1;59(23):5908-5911.
Kato, Shunsuke ; Shimada, Akira ; Osada, Motonobu ; Ikawa, Shuntaro ; Obinata, Masuo ; Nakagawara, Akira ; Kanamaru, Ryunosuke ; Ishioka, Chikashi. / Effects of p51/p63 missense mutations on transcriptional activities of p53 downstream gene promoters. In: Cancer Research. 1999 ; Vol. 59, No. 23. pp. 5908-5911.
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