K63-linked polyubiquitination of transcription factor IRF1 is essential for IL-1-induced production of chemokines CXCL10 and CCL5.
In: Nature Immunology, Jg. 15 (2014-03-01), Heft 3, S. 231-238
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Zugriff:
Although interleukin 1 (IL-1) induces expression of the transcription factor IRF1 (interferon-regulatory factor 1), the roles of IRF1 in immune and inflammatory responses and mechanisms of its activation remain elusive. Here we found that IRF1 was essential for IL-1-induced expression of the chemokines CXCL10 and CCL5, which recruit mononuclear cells into sites of sterile inflammation. Newly synthesized IRF1 acquired Lys63 (K63)-linked polyubiquitination mediated by the apoptosis inhibitor cIAP2 that was enhanced by the bioactive lipid S1P. In response to IL-1, cIAP2 and the sphingosine kinase SphK1 (the enzyme that generates S1P) formed a complex with IRF1, which led to its activation. Thus, IL-1 triggered a hitherto unknown signaling cascade that controlled the induction of IRF1-dependent genes that encode molecules important for sterile inflammation. [ABSTRACT FROM AUTHOR]
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K63-linked polyubiquitination of transcription factor IRF1 is essential for IL-1-induced production of chemokines CXCL10 and CCL5.
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Autor/in / Beteiligte Person: | Harikumar, Kuzhuvelil B ; Yester, Jessie W ; Surace, Michael J ; Oyeniran, Clement ; Price, Megan M ; Huang, Wei-Ching ; Hait, Nitai C ; Allegood, Jeremy C ; Yamada, Akimitsu ; Kong, Xiangqian ; Lazear, Helen M ; Bhardwaj, Reetika ; Takabe, Kazuaki ; Diamond, Michael S ; Luo, Cheng ; Milstien, Sheldon ; Spiegel, Sarah ; Kordula, Tomasz |
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Zeitschrift: | Nature Immunology, Jg. 15 (2014-03-01), Heft 3, S. 231-238 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 1529-2908 (print) |
DOI: | 10.1038/ni.2810 |
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