The screening of the second-site suppressor mutations of the common p53 mutants

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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Second-site suppressor (SSS) mutations in p53 found by random mutagenesis have shown to restore the inactivated function of some tumor-derived p53. To screen novel SSS mutations against common mutant p53s, intragenic second-site (SS) mutations were introduced into mutant p53 cDNA in a comprehensive manner by using a p53 missense mutation library. The resulting mutant p53s with background and SS mutations were assayed for their ability to restore the p53 transactivation function in both yeast and human cell systems. We identified 12 novel SSS mutations including H178Y against a common mutation G245S. Surprisingly, the G245S phenotype is rescued when coexpressed with p53 bearing the H178Y mutation. This result indicated that there is a possibility that intragenic suppressor mutations might restore the protein function in an intermolecular manner. The intermolecular mechanism may lead to novel strategies for restoring inactivated p53 function and tumor suppression in cancer treatment.

Original languageEnglish
Pages (from-to)559-566
Number of pages8
JournalInternational Journal of Cancer
Volume121
Issue number3
DOIs
Publication statusPublished - 2007 Aug 1

Keywords

  • Intragenic suppressor
  • Second-site suppressor mutation
  • Transactivation
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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