Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance.
NF-κB
PIDDosome
centrosome
immunosurveillance
sterile inflammation
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
16 10 2023
16 10 2023
Historique:
revised:
01
07
2023
received:
13
01
2023
accepted:
18
07
2023
medline:
23
10
2023
pubmed:
2
8
2023
entrez:
2
8
2023
Statut:
ppublish
Résumé
Unscheduled increases in ploidy underlie defects in tissue function, premature aging, and malignancy. A concomitant event to polyploidization is the amplification of centrosomes, the main microtubule organization centers in animal cells. Supernumerary centrosomes are frequent in tumors, correlating with higher aggressiveness and poor prognosis. However, extra centrosomes initially also exert an onco-protective effect by activating p53-induced cell cycle arrest. If additional signaling events initiated by centrosomes help prevent pathology is unknown. Here, we report that extra centrosomes, arising during unscheduled polyploidization or aberrant centriole biogenesis, induce activation of NF-κB signaling and sterile inflammation. This signaling requires the NEMO-PIDDosome, a multi-protein complex composed of PIDD1, RIPK1, and NEMO/IKKγ. Remarkably, the presence of supernumerary centrosomes suffices to induce a paracrine chemokine and cytokine profile, able to polarize macrophages into a pro-inflammatory phenotype. Furthermore, extra centrosomes increase the immunogenicity of cancer cells and render them more susceptible to NK-cell attack. Hence, the PIDDosome acts as a dual effector, able to engage not only the p53 network for cell cycle control but also NF-κB signaling to instruct innate immunity.
Identifiants
pubmed: 37530438
doi: 10.15252/embj.2023113510
pmc: PMC10577638
doi:
Substances chimiques
NF-kappa B
0
Tumor Suppressor Protein p53
0
PIDD1 protein, human
0
Banques de données
GEO
['GSE235120']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e113510Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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