title: Treatment with IL-17 prolongs the half-life of chemokine CXCL1 mRNA via the adaptor TRAF5 and the splicing-regulatory factor SF2 (ASF).
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).
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: Dongxu
authors.initials: D
authors.lastname: Sun
authors.forename: Michael
authors.initials: M
authors.lastname: Novotny
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bulek
authors.forename: Caini
authors.initials: C
authors.lastname: Liu
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.forename: Thomas
authors.initials: T
authors.lastname: Hamilton
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017398:Alternative Splicing; D000818:Animals; D054360:Chemokine CXCL1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction / Q000276:immunology*; D048015:TNF Receptor-Associated Factor 5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D054360:Chemokine CXCL1; D020381:Interleukin-17; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C499176:T2bp protein, mouse; D048015:TNF Receptor-Associated Factor 5; C515963:Traf3ip2 protein, mouse; D000068103:Serine-Arginine Splicing Factors