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

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

Life science alliance (2023-02-07)
Mélanie Bodnar-Wachtel, Anne-Laure Huber, Julie Gorry, Sabine Hacot, Delphine Burlet, Laetitia Gérossier, Baptiste Guey, Nadège Goutagny, Birke Bartosch, Elise Ballot, Julie Lecuelle, Caroline Truntzer, François Ghiringhelli, Bénédicte F Py, Yohann Couté, Annabelle Ballesta, Sylvie Lantuejoul, Janet Hall, Agnès Tissier, Virginie Petrilli
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 resist apoptosis induced by acute genotoxic stress. Interestingly, NLRP3 expression is down-regulated in non-small cell lung cancers and breast cancers, and its expression positively correlates with patient overall survival. Our findings identify a novel non-immune function for NLRP3 in maintaining genome integrity and strengthen the concept of a functional link between innate immunity and DNA damage sensing pathways to maintain cell integrity.

MATERIALS
Product Number
Brand
Product Description

Millipore
ANTI-FLAG® antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-NLRP3 Antibody, from rabbit, purified by affinity chromatography
Millipore
Monoclonal Anti-HA−Agarose antibody produced in mouse, clone HA-7, purified immunoglobulin, PBS suspension
Millipore
ANTI-FLAG® M2 Affinity Gel, purified immunoglobulin, buffered aqueous glycerol solution