Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses.

ABSTRACT: Engineered p53 mutant mice are valuable tools for delineating p53 functions in tumor suppression and cancer therapy. Here, we have introduced the R178E mutation into the Trp53 gene of mice to specifically ablate the cooperative nature of p53 DNA binding. Trp53^R178E mice show no detectable target gene regulation and, at first sight, are largely indistinguishable from Trp53^-/- mice. Surprisingly, stabilization of p53^R178E in Mdm2^-/- mice nevertheless triggers extensive apoptosis, indicative of residual wild-type activities. Although this apoptotic activity suffices to trigger lethality of Trp53^R178E ;Mdm2^-/- embryos, it proves insufficient for suppression of spontaneous and oncogene-driven tumorigenesis. Trp53^R178E

SUBMITTER: Timofeev O 

PROVIDER: S-EPMC6792016 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature