Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
21
04
2022
revised:
20
01
2023
accepted:
20
01
2023
entrez:
6
2
2023
pubmed:
7
2
2023
medline:
9
2
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36746533
pii: 6/4/e202201494
doi: 10.26508/lsa.202201494
pmc: PMC9904227
pii:
doi:
Substances chimiques
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
ATM protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Bodnar-Wachtel et al.
Références
Genes Dev. 2001 Jan 1;15(1):50-65
pubmed: 11156605
Cell. 2014 Aug 14;158(4):929-944
pubmed: 25109877
Genes Dev. 2003 Sep 15;17(18):2233-8
pubmed: 12952892
Nat Rev Mol Cell Biol. 2010 Mar;11(3):220-8
pubmed: 20177397
Nature. 2005 Apr 14;434(7035):864-70
pubmed: 15829956
Immunity. 2016 Jul 19;45(1):106-18
pubmed: 27421701
Mol Cell. 2004 Dec 22;16(6):1017-25
pubmed: 15610743
Methods. 2020 Mar 15;175:66-71
pubmed: 31499160
Curr Biol. 2000 Jul 27-Aug 10;10(15):886-95
pubmed: 10959836
Cold Spring Harb Perspect Biol. 2013 Mar 01;5(3):a012914
pubmed: 23335075
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Cell. 2010 Mar 19;140(6):821-32
pubmed: 20303873
Nat Immunol. 2015 Aug;16(8):859-70
pubmed: 26098997
EMBO J. 2019 Oct 4;38(21):e102718
pubmed: 31544964
Nature. 2010 Aug 12;466(7308):869-73
pubmed: 20668451
Science. 1998 Sep 11;281(5383):1677-9
pubmed: 9733515
Br J Cancer. 2015 Mar 17;112(6):1059-66
pubmed: 25742469
Nature. 2003 Jan 30;421(6922):499-506
pubmed: 12556884
Nature. 2006 Mar 9;440(7081):228-32
pubmed: 16407890
Nat Rev Immunol. 2007 Jan;7(1):31-40
pubmed: 17186029
Nature. 2008 Oct 23;455(7216):1069-75
pubmed: 18948947
Brief Bioinform. 2021 Jul 20;22(4):
pubmed: 33212483
Nat Biotechnol. 2020 Jun;38(6):675-678
pubmed: 32444850
Adv Cancer Res. 2010;108:73-112
pubmed: 21034966
Science. 2002 May 3;296(5569):922-7
pubmed: 11934988
Nucleic Acids Res. 2014 Jul;42(12):7666-80
pubmed: 24928858
Curr Protoc Cell Biol. 2010 Jun;Chapter 3:Unit3.36
pubmed: 20521233
EMBO J. 2006 Oct 18;25(20):4952-62
pubmed: 17024184
Genome Biol. 2008 Apr 30;9(4):216
pubmed: 18466635
Cell Rep. 2018 Apr 03;23(1):239-254.e6
pubmed: 29617664
Curr Opin Oncol. 2017 Jan;29(1):35-40
pubmed: 27875342
PLoS One. 2008 Aug 06;3(8):e2888
pubmed: 18682804
Oncotarget. 2016 Sep 6;7(36):57714-57725
pubmed: 27259260
PLoS Pathog. 2015 Jun 29;11(6):e1005030
pubmed: 26121674
Nat Immunol. 2014 Jun;15(6):538-45
pubmed: 24777530
Nat Rev Drug Discov. 2018 Aug;17(8):588-606
pubmed: 30026524
Nat Immunol. 2016 Mar;17(3):250-8
pubmed: 26642356
Nature. 2012 Oct 25;490(7421):539-42
pubmed: 22885697
Cancer Res. 2004 Dec 15;64(24):9027-34
pubmed: 15604268
Nature. 2018 Nov;563(7729):131-136
pubmed: 30356214
Trends Immunol. 2005 Aug;26(8):447-54
pubmed: 15967716
Mol Cell. 2001 Mar;7(3):683-94
pubmed: 11463392
Cell. 2012 Sep 14;150(6):1107-20
pubmed: 22980975
Clin Cancer Res. 2010 Jun 1;16(11):2979-88
pubmed: 20404006
Nature. 2015 Oct 29;526(7575):660-5
pubmed: 26375003
Cancer Immunol Res. 2017 Feb;5(2):94-99
pubmed: 28093447
Joint Bone Spine. 2007 Dec;74(6):571-6
pubmed: 17714972
Cancer Res. 2001 Mar 1;61(5):1849-54
pubmed: 11280737
Nature. 2012 Sep 27;489(7417):519-25
pubmed: 22960745
Nat Genet. 1995 Dec;11(4):428-33
pubmed: 7493024
Science. 2016 Nov 11;354(6313):765-768
pubmed: 27846608
Histopathology. 2003 Oct;43(4):347-53
pubmed: 14511253
Nat Rev Immunol. 2016 Jul;16(7):407-20
pubmed: 27291964
Cell Death Differ. 2007 Sep;14(9):1583-9
pubmed: 17599094
J Biol Chem. 2001 Nov 9;276(45):42462-7
pubmed: 11571274
PLoS Comput Biol. 2020 Jan 27;16(1):e1007218
pubmed: 31986133