NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component

The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines including IL-1β and IL-18. We show that NLRP3 inflammasome activation is restricted to interphase of the cell cycle by NEK7, a serine/threonine kinase previously implicated in mitosi...

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Detalles Bibliográficos
Autores principales: Shi, Hexin, Wang, Ying, Li, Xiaohong, Zhan, Xiaoming, Tan, Miao, Fina, Maggy, Su, Lijing, Pratt, David, Bu, Chun Hui, Hildebrand, Sara, Lyon, Stephen, Scott, Lindsay, Quan, Jiexia, Sun, Qihua, Russell, Jamie, Arnett, Stephanie, Jurek, Peter, Chen, Ding, Kravchenko, Vladimir V., Mathison, John C., Moresco, Eva Marie Y., Monson, Nancy L., Ulevitch, Richard J., Beutler, Bruce
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862588/
https://www.ncbi.nlm.nih.gov/pubmed/26642356
http://dx.doi.org/10.1038/ni.3333
Descripción
Sumario:The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines including IL-1β and IL-18. We show that NLRP3 inflammasome activation is restricted to interphase of the cell cycle by NEK7, a serine/threonine kinase previously implicated in mitosis. NLRP3 inflammasome activation requires NEK7, which binds to the NLRP3 leucine-rich repeat domain in a kinase-independent manner downstream from the induction of mitochondrial ROS. This interaction is necessary for NLRP3-ASC complex formation, ASC oligomerization, and caspase-1 activation. NEK7 promotes the NLRP3-dependent cellular inflammatory response to intraperitoneal monosodium urate challenge, and the development of experimental autoimmune encephalitis in mice. Our findings suggest NEK7 serves as a cellular switch that enforces mutual exclusivity between the inflammasome response and cell division.

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