Oncogenic and teratogenic effects of <i>Trp53</i>^Y217C, an inflammation-prone mouse model of the human hotspot mutant <i>TP53</i>^Y220C.

ABSTRACT: Missense 'hotspot' mutations localized in six p53 codons account for 20% of TP53 mutations in human cancers. Hotspot p53 mutants have lost the tumor suppressive functions of the wildtype protein, but whether and how they may gain additional functions promoting tumorigenesis remain controversial. Here, we generated Trp53^Y217C, a mouse model of the human hotspot mutant TP53^Y220C. DNA damage responses were lost in Trp53^Y217C/Y217C (Trp53^YC/YC) cells, and Trp53^YC/YC fibroblasts exhibited increased chromosome instability compared to Trp53^-/- cells. Furthermore, Trp53^YC/YC male mice died earlier than Trp53^-/- males, with more aggressive thymic lym

SUBMITTER: Jaber S 

PROVIDER: S-EPMC11996178 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature