Abstract
Interleukin 17 (IL-17) promotes the expression of chemokines and cytokines via the induction of gene transcription and post-transcriptional stabilization of mRNA. We show here that IL-17 enhanced the stability of chemokine CXCL1 mRNA and other mRNAs through a pathway that involved the adaptor Act1, the adaptors TRAF2 or TRAF5 and the splicing factor SF2 (also known as alternative splicing factor (ASF)). TRAF2 and TRAF5 were necessary for IL-17 to signal the stabilization of CXCL1 mRNA. Furthermore, IL-17 promoted the formation of complexes of TRAF5-TRAF2, Act1 and SF2 (ASF). Overexpression of SF2 (ASF) shortened the half-life of CXCL1 mRNA, whereas depletion of SF2 (ASF) prolonged it. SF2 (ASF) bound chemokine mRNA in unstimulated cells, whereas the SF2 (ASF)-mRNA interaction was much lower after stimulation with IL-17. Our findings define an IL-17-induced signaling pathway that links to the stabilization of selected mRNA species through Act1, TRAF2-TRAF5 and the RNA-binding protein SF2 (ASF).
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology
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Adaptor Proteins, Signal Transducing / metabolism*
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Alternative Splicing
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Animals
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Chemokine CXCL1 / genetics
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Chemokine CXCL1 / immunology
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Chemokine CXCL1 / metabolism*
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Female
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Half-Life
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HeLa Cells
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Humans
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Inflammation / genetics
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Inflammation / immunology*
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Inflammation / metabolism
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Interleukin-17* / immunology
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Interleukin-17* / metabolism
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Interleukin-17* / pharmacology
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Mice
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Mice, Knockout
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology
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Nuclear Proteins / metabolism*
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RNA Processing, Post-Transcriptional
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RNA Stability / drug effects
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RNA, Messenger
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / immunology
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RNA-Binding Proteins / metabolism*
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Serine-Arginine Splicing Factors
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Signal Transduction / immunology*
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TNF Receptor-Associated Factor 5 / genetics
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TNF Receptor-Associated Factor 5 / immunology
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TNF Receptor-Associated Factor 5 / metabolism*
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Th17 Cells / immunology*
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Th17 Cells / metabolism
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Transcription, Genetic
Substances
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Adaptor Proteins, Signal Transducing
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Chemokine CXCL1
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Interleukin-17
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Nuclear Proteins
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RNA, Messenger
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RNA-Binding Proteins
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T2bp protein, mouse
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TNF Receptor-Associated Factor 5
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Traf3ip2 protein, mouse
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Serine-Arginine Splicing Factors