Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress.

ABSTRACT: NLRP3 is a pattern recognition receptor with a well-documented role in inducing inflammasome assembly in response to cellular stress. Deregulation of its activity leads to many inflammatory disorders including gouty arthritis, Alzheimer disease, and cancer. Whereas its role in the context of cancer has been mostly explored in the immune compartment, whether NLRP3 exerts functions unrelated to immunity in cancer development remains unexplored. Here, we demonstrate that NLRP3 interacts with the ATM kinase to control the activation of the DNA damage response, independently of its inflammasome activity. NLRP3 down-regulation in both broncho- and mammary human epithelial cells significantly impairs ATM pathway activation, leading to lower p53 activation, and provides cells with the ability to r

SUBMITTER: Bodnar-Wachtel M 

PROVIDER: S-EPMC9904227 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature