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NLRP3 controls ATM activation in response to DNA damage

Abstract : The DNA damage response (DDR) is essential to preserve genomic integrity and acts as a barrier to cancer. The ATM pathway orchestrates the cellular response to DNA double strand breaks (DSBs), and its attenuation is frequent during tumorigenesis. Here, we show that NLRP3, a Pattern Recognition Receptor known for its role in the inflammasome complex formation, interacts with the ATM kinase to control the early phase of DDR, independently of its inflammasome activity. NLRP3 down-regulation in human bronchial epithelial cells impairs ATM pathway activation as shown by an altered ATM substrate phosphorylation profile, and due to impaired p53 activation, confers resistance to acute genomic stress. Moreover, we found that NLRP3 is down-regulated in Non-Small Cell Lung Cancer (NSCLC) tissues and NLRP3 expression is correlated with patient overall survival. NLRP3 re-expression in NSCLC cells restores appropriate ATM signaling. Our findings identify a non-immune function for NLRP3 in genome integrity surveillance and strengthen the concept of a functional link between innate immunity and DNA damage sensing pathways.
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Preprints, Working Papers, ...
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https://hal.archives-ouvertes.fr/hal-03093041
Contributor : Virginie Petrilli <>
Submitted on : Tuesday, January 5, 2021 - 11:11:22 AM
Last modification on : Wednesday, February 24, 2021 - 11:26:05 AM
Long-term archiving on: : Wednesday, April 7, 2021 - 9:28:50 AM

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CORR_NLRP3 ATM 14_04_2020.pdf
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Mélanie Bodnar-Wachtel, Anne-Laure Huber, Julie Gorry, Sabine Hacot, Laetitia Gerossier, et al.. NLRP3 controls ATM activation in response to DNA damage. 2021. ⟨hal-03093041⟩

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