Investigation of Functional Roles of New p53 Family Members - p73, p51, and p40 in Brain Tumors

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In this research project, we investigated functional roles of new p53 family members - p73, p51, and p40 in human brain tumors. We developed new yeast-based assays to measure transcriptional activity of p73 and p63 and applied to brain tumors. As the results, we obtained the followings:1) We applied a newly developed yeast p73 functional assay to a total of 52 cases of glioblastoma and meningioma, and found no p73 mutation in these tumors. We showed, however, that expression of α, β, γ, and ε isoforms of p73 correlates with malignancy of meningioma (Brain Pathol., 2001).2) Recessive p53 mutants are known to specifically inhibit p73. We showed an allele specific selection of Arg72, which strongly inhibits p73, by recessive p53 mutation, but not by dominant negative p53 mutations (Carcinogenesis, 2001).3) We reported transcriptional activity of p73 mutants - P405R and P425L found in human tumors (Oncogene, 2001).4) We developed a quantitative transcriptional assay for p53, p73, and p63 tumor suppressors, and will publish the results as soon.