Inactivation of Mdm2 restores apoptosis proficiency of cooperativity mutant p53 in vivo.

ABSTRACT: TP53 mutations are found in 50% of all cancers and mutated TP53 status is considered poor for treatment. However, some TP53 mutations exhibit only partial loss-of-function (LOF), meaning they retain residual transcriptional and non-transcriptional activities that are potentially beneficial for therapy. Earlier we have characterized a knock-in mouse model for the partial LOF mutant Trp53^E177R (p53RR). Reduced DNA binding cooperativity of this mutant led to the loss of p53-dependent apoptosis, while p53 functions in cell cycle control, senescence, metabolism, and antioxidant defense remained intact. Concomitantly, tumor suppression was evident but strongly compromised compared to wild-type mice. Here we used the Trp53^E177R mouse as a m

SUBMITTER: Klimovich B 

PROVIDER: S-EPMC6927723 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature