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Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress
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(2023) Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress. Life Science Alliance, 6 (4). e202201494. doi:10.26508/lsa.202201494 ISSN 2575-1077.
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WRAP-Inflammasome-independent-NLRP3-function-enforces-ATM-activity-in-response-to-genotoxic-stress-Ballesta-2023.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2450Kb) | Preview |
Official URL: http://dx.doi.org/10.26508/lsa.202201494
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.
Item Type: | Journal Article | |||||||||||||||||||||||||||||||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RA Public aspects of medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Inflammation -- Molecular aspects, Cell receptors, Immunity , Protein kinases -- Inhibitors , Genetic toxicology | |||||||||||||||||||||||||||||||||
Journal or Publication Title: | Life Science Alliance | |||||||||||||||||||||||||||||||||
Publisher: | Life Science Alliance | |||||||||||||||||||||||||||||||||
ISSN: | 2575-1077 | |||||||||||||||||||||||||||||||||
Official Date: | April 2023 | |||||||||||||||||||||||||||||||||
Dates: |
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Volume: | 6 | |||||||||||||||||||||||||||||||||
Number: | 4 | |||||||||||||||||||||||||||||||||
Number of Pages: | 14 | |||||||||||||||||||||||||||||||||
Article Number: | e202201494 | |||||||||||||||||||||||||||||||||
DOI: | 10.26508/lsa.202201494 | |||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 7 March 2023 | |||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 8 March 2023 | |||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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