Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance.

Autor: Garcia-Carpio I; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Braun VZ; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Weiler ES; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Leone M; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Niñerola S; Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, Alicante, Spain., Barco A; Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, Alicante, Spain., Fava LL; Armenise-Harvard Laboratory of Cell Division, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Trento, Italy., Villunger A; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2023 Oct 16; Vol. 42 (20), pp. e113510. Date of Electronic Publication: 2023 Aug 02.
DOI: 10.15252/embj.2023113510
Abstrakt: 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.
(© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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