title: The screening of the second-site suppressor mutations of the common p53 mutants.
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.
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, and Tohoku University Hospital, Tohoku University, Sendai, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Otsuka
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kato
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kakudo
authors.forename: Satsuki
authors.initials: S
authors.lastname: Mashiko
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shibata
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004252:DNA Mutational Analysis; D016158:Genes, p53; D006801:Humans; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013489:Suppression, Genetic; D015533:Transcriptional Activation; D014162:Transfection