Endogenous p53 inhibitor TIRR dissociates systemic metabolic health from oncogenic activity.

ABSTRACT: It is unclear whether metabolic health corresponds to reduced oncogenesis or vice versa. We study Tudor-interacting repair regulator (TIRR), an inhibitor of p53 binding protein 1 (53BP1)-mediated p53 activation, and the physiological consequences of enhancing tumor suppressor activity. Deleting TIRR selectively activates p53, significantly protecting against cancer but leading to a systemic metabolic imbalance in mice. TIRR-deficient mice are overweight and insulin resistant, even under normal chow diet. Similarly, reduced TIRR expression in human adipose tissue correlates with higher BMI and insulin resistance. Despite the metabolic challenges, TIRR loss improves p53 heterozygous (p53^HET) mouse survival and correlates with enhanced progression-free survival in patients with var

SUBMITTER: Tsaousidou E 

PROVIDER: S-EPMC11325268 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature