Oleg Timofeev, Katharina Schlereth, Michael Wanzel, Attila Braun, Bernhard Nieswandt, Axel Pagenstecher, Andreas Rosenwald, Hans-Peter Elsässer, Thorsten Stiewe
Abstract:Four molecules of the tumor suppressor p53 assemble to cooperatively bind proapoptotic target genes. The structural basis for cooperativity consists of interactions between adjacent DNA binding domains. Mutations at the interaction interface that compromise cooperativity were identified in cancer patients, suggesting a requirement of cooperativity for tumor suppression. We report on an analysis of cooperativity mutant p53E177R mice. Apoptotic functions of p53 triggered by DNA damage and oncogenes were abolishe…
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