دورية أكاديمية
Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance
| العنوان: | Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance |
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| المؤلفون: | Garcia-Carpio, Irmina, Braun, Vincent Z, Weiler, Elias S, Leone, Marina, Niñerola, Sergio, Barco, Angel, Fava, Luca, Villunger, Andreas |
| المساهمون: | Garcia-Carpio, Irmina, Braun, Vincent Z, Weiler, Elias S, Leone, Marina, Niñerola, Sergio, Barco, Angel, Fava, Luca, Villunger, Andreas |
| سنة النشر: | 2023 |
| المجموعة: | Università degli Studi di Trento: CINECA IRIS |
| مصطلحات موضوعية: | NF-κB, PIDDosome, centrosome, immunosurveillance, sterile inflammation |
| الوصف: | 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-?B signaling and sterile inflammation. This signaling requires the NEMO-PIDDosome, a multi-protein complex composed of PIDD1, RIPK1, and NEMO/IKK?. 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-?B signaling to instruct innate immunity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/37530438; info:eu-repo/semantics/altIdentifier/wos/WOS:001041474300001; volume:42; issue:20; firstpage:e11351001; lastpage:e11351022; numberofpages:22; journal:EMBO JOURNAL; https://hdl.handle.net/11572/402197Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85166659847 |
| DOI: | 10.15252/embj.2023113510 |
| الإتاحة: | https://doi.org/10.15252/embj.2023113510Test https://hdl.handle.net/11572/402197Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6ED3FA5F |
| قاعدة البيانات: | BASE |
| DOI: | 10.15252/embj.2023113510 |
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