Details
- Autor(en) / Beteiligte
- Titel
- Treatment with IL-17 prolongs the half-life of chemokine CXCL1 mRNA via the adaptor TRAF5 and the splicing-regulatory factor SF2 (ASF)
- Ist Teil von
- Nature immunology, 2011-09, Vol.12 (9), p.853
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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).
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1529-2916DOI: 10.1038/ni.2081Titel-ID: cdi_pubmed_primary_21822258
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - genetics, Adaptor Proteins, Signal Transducing - immunology, Adaptor Proteins, Signal Transducing - metabolism, Alternative Splicing, Animals, Chemokine CXCL1 - genetics, Chemokine CXCL1 - immunology, Chemokine CXCL1 - metabolism, Female, Half-Life, HeLa Cells, Humans, Inflammation - genetics, Inflammation - immunology, Inflammation - metabolism, Interleukin-17 - immunology, Interleukin-17 - metabolism, Interleukin-17 - pharmacology, Mice, Mice, Knockout, Nuclear Proteins - genetics, Nuclear Proteins - immunology, Nuclear Proteins - metabolism, RNA Processing, Post-Transcriptional, RNA Stability - drug effects, RNA, Messenger, RNA-Binding Proteins - genetics, RNA-Binding Proteins - immunology, RNA-Binding Proteins - metabolism, Serine-Arginine Splicing Factors, Signal Transduction - immunology, Th17 Cells - immunology, Th17 Cells - metabolism, TNF Receptor-Associated Factor 5 - genetics, TNF Receptor-Associated Factor 5 - immunology, TNF Receptor-Associated Factor 5 - metabolism, Transcription, Genetic