α-Ketoglutarate links p53 to cell fate during tumour suppression.

ABSTRACT: The tumour suppressor TP53 is mutated in the majority of human cancers, and in over 70% of pancreatic ductal adenocarcinoma (PDAC)^1,2. Wild-type p53 accumulates in response to cellular stress, and regulates gene expression to alter cell fate and prevent tumour development². Wild-type p53 is also known to modulate cellular metabolic pathways³, although p53-dependent metabolic alterations that constrain cancer progression remain poorly understood. Here we find that p53 remodels cancer-cell metabolism to enforce changes in chromatin and gene expression that favour a premalignant cell fate. Restoring p53 function in cancer cells derived from KRAS-mutant mouse models of PDAC leads to the accumulation of α-ketoglutarate (αKG, also known as 2-oxoglutarate), a meta

SUBMITTER: Morris JP 

PROVIDER: S-EPMC6830448 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature