Interleukin 17 (IL-17) is a proinflammatory cytokine that promotes the expression of different cytokines and chemokines via the induction of gene transcription and the post-transcriptional stabilization of mRNAs. Here 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. Interleukin 17 stimulation promotes the formation of a complex between CIKS and DDX3X, this interaction requires the helicase domain of DDX3X but not its ATPase activity. DDX3X knock-down decreases the IL-17-induced stability of Zc3h12a without affecting the stability of other mRNAs. IKKε, TRAF2 and TRAF5 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.
Our results indicate NGAL as a novel target of nuclear factor-κB prometastatic activity in thyroid cancer through enhancement of MMP-9 enzymatic activity.
The demographic tendency in industrial countries to delay childbearing , coupled with the maternal age effect in common chromosomal aneuploidies and the risk to the fetus of invasive prenatal diagnosis, are potent drivers for the development of strategies for noninvasive prenatal diagnosis. One breakthrough has been the discovery of differentially methylated cell-free fetal DNA in the maternal circulation. We describe novel bisulfite conversion-and methylationsensitive enzyme digestion DNA methylation-related approaches that we used to diagnose Turner syndrome from first trimester samples. We used an Xlinked marker , EF3 , and an autosomal marker, RASSF1A , to discriminate between placental and maternal blood cell DNA using real-time methylationspecific PCR after bisulfite conversion and real-time PCR after methylation-sensitive restriction digestion. By normalizing EF3 amplifications versus RASSF1A outputs , we were able to calculate sex chromosome/ autosome ratios in chorionic villus samples , thus permitting us to correctly diagnose Turner syndrome. The identification of this new marker coupled with the strategy outlined here may be instrumental in the development of an efficient , noninvasive method of diagnosis of sex chromosome aneuploidies in plasma
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