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.

CIKS/DDX3X interaction controls the stability of the Zc3h12a mRNA induced by IL-17 / Somma, Domenico; Mastrovito, P.; Grieco, M.; Lavorgna, A.; Pignalosa, A.; Formisano, L.; Salzano, A. M.; Scaloni, A.; Pacifico, F.; Siebenlist, U.; Leonardi, Antonio. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 194:7(2015), pp. 3286-3297. [10.4049/jimmunol.1401589]

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

SOMMA, DOMENICO;Formisano L.;LEONARDI, ANTONIO
2015

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.
2015
CIKS/DDX3X interaction controls the stability of the Zc3h12a mRNA induced by IL-17 / Somma, Domenico; Mastrovito, P.; Grieco, M.; Lavorgna, A.; Pignalosa, A.; Formisano, L.; Salzano, A. M.; Scaloni, A.; Pacifico, F.; Siebenlist, U.; Leonardi, Antonio. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 194:7(2015), pp. 3286-3297. [10.4049/jimmunol.1401589]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/602193
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