CIKS/DDX3X interaction controls the stability of the Zc3h12a mRNA Induced by IL-17

Somma, D. et al. (2015) CIKS/DDX3X interaction controls the stability of the Zc3h12a mRNA Induced by IL-17. Journal of Immunology, 194(7), pp. 3286-3294. (doi: 10.4049/jimmunol.1401589) (PMID:25710910) (PMCID:PMC4369453)

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Abstract

IL-17 is a proinflammatory cytokine that promotes the expression of different cytokines and chemokines via the induction of gene transcription and the posttranscriptional stabilization of mRNAs. In this study, we show that IL-17 increases the half-life of the Zc3h12a mRNA via interaction of the adaptor protein CIKS with the DEAD box protein DDX3X. IL-17 stimulation promotes the formation of a complex between CIKS and DDX3X, and this interaction requires the helicase domain of DDX3X but not its ATPase activity. DDX3X knockdown decreases the IL-17–induced stability of Zc3h12a without affecting the stability of other mRNAs. IKKε, TNFR-associated factor 2, and TNFR-associated factor 5 were also required to mediate the IL-17–induced Zc3h12a stabilization. DDX3X directly binds the Zc3h12a mRNA after IL-17 stimulation. Collectively, our findings define a novel, IL-17–dependent mechanism regulating the stabilization of a selected mRNA.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Somma, Domenico
Authors: Somma, D., Mastrovito, P., Grieco, M., Lavorgna, A., Pignalosa, A., Formisano, L., Salzano, A. M., Scaloni, A., Pacifico, F., Siebenlist, U., and Leonardi, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606
Published Online:20 February 2015

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