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- W2055422821 abstract "The low molecular weight compound PRIMA-1 and the structural analog PRIMA-1MET, also named APR-246, reactivate mutant p53 through covalent binding to the core domain and induce apoptosis in tumor cells. Here, we asked whether PRIMA-1MET/APR-246 can rescue mutant forms of the p53 family members p63 and p73 that share high sequence homology with p53. We found that PRIMA-1MET/APR-246 can restore the pro-apoptotic function to mutant TAp63γ and TAp73β in tumor cells but has less effect on TAp73α. Moreover, PRIMA-1MET/APR-246-stimulated DNA binding of mutant TAp63γ and induced expression of the p53/p63/p73 downstream targets p21 and Noxa. The reactivation of mutant p53, p63 and p73 by PRIMA-1MET/APR-246 indicates a common mechanism, presumably involving homologous structural elements in the p53 family proteins. Our findings may open avenues for therapeutic intervention in human developmental disorders with mutations in p63." @default.
- W2055422821 created "2016-06-24" @default.
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- W2055422821 date "2010-09-06" @default.
- W2055422821 modified "2023-10-17" @default.
- W2055422821 title "PRIMA-1MET/APR-246 targets mutant forms of p53 family members p63 and p73" @default.
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- W2055422821 doi "https://doi.org/10.1038/onc.2010.382" @default.
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