| Autor: |
Rökaeus, N, Shen, J, Eckhardt, I, Bykov, V J N, Wiman, K G, Wilhelm, M T |
| Předmět: |
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| Zdroj: |
Oncogene; 12/9/2010, Vol. 29 Issue 49, p6442-6451, 10p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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