Mechanistic basis for impaired ferroptosis in cells expressing the African-centric S47 variant of p53.

ABSTRACT: A population-restricted single-nucleotide coding region polymorphism (SNP) at codon 47 exists in the human TP53 gene (P47S, hereafter P47 and S47). In studies aimed at identifying functional differences between these variants, we found that the African-specific S47 variant associates with an impaired response to agents that induce the oxidative stress-dependent, nonapoptotic cell death process of ferroptosis. This phenotype is manifested as a greater resistance to glutamate-induced cytotoxicity in cultured cells as well as increased carbon tetrachloride-mediated liver damage in a mouse model. The differential ferroptotic responses associate with intracellular antioxidant differences between P47 and S47 cells, including elevated abundance of the low molecular weight thiols coenzyme A

SUBMITTER: Leu JI 

PROVIDER: S-EPMC6486733 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature