Mis-splicing Drives Loss of Function of p53^E224D Point Mutation.

ABSTRACT:

Background

Tp53 is the most commonly mutated gene in cancer. Canonical Tp53 DNA damage response pathways are well characterized and classically thought to underlie the tumor suppressive effect of Tp53. Challenging this dogma, mouse models have revealed that p53 driven apoptosis and cell cycle arrest are dispensable for tumor suppression. Here, we investigated the inverse context of a p53 mutation predicted to drive expression of canonical targets, but is detected in human cancer.

Methods

We established a novel mouse model with a single base pair mutation (GAG>GAC, p53^E221D) in the DNA-Binding domain that has wild-type function in screening assays, but is paradoxically found in human cancer in Li-Fraumeni syndrome. Using mouse p53^E221D and the analogous

SUBMITTER: Lock IC 

PROVIDER: S-EPMC10418211 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature