@article{d9a3cf11b51e46a6b9cce5eafc43f8cd,
title = "K63-linked polyubiquitination of transcription factor IRF1 is essential for IL-1-induced production of chemokines CXCL10 and CCL5",
abstract = "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.",
author = "Harikumar, \{Kuzhuvelil B.\} and Yester, \{Jessie W.\} and Surace, \{Michael J.\} and Clement Oyeniran and Price, \{Megan M.\} and Huang, \{Wei Ching\} and Hait, \{Nitai C.\} and Allegood, \{Jeremy C.\} and Akimitsu Yamada and Xiangqian Kong and Lazear, \{Helen M.\} and Reetika Bhardwaj and Kazuaki Takabe and Diamond, \{Michael S.\} and Cheng Luo and Sheldon Milstien and Sarah Spiegel and Tomasz Kordula",
note = "Funding Information: We thank B. Darnay (MD Anderson) for the plasmid encoding wild-type TRAF2; X.-Y. Wang (Virginia Commonwealth University) for the plasmid encoding histidine-tagged TRAF6; Z. Chen (University of Texas Southwestern Medical Center) for the plasmids encoding hemagglutinin-tagged ubiquitins; C. Duckett (University of Michigan) for the plasmid encoding hemagglutinin-tagged cIAP2 and for Birc3−/− MEFs; X. Wang (University of Texas Southwestern Medical Center) for the mimetic SMAC; R. Proia (US National Institutes of Health) for Sphk1−/− mice; A. Larner (Virginia Commonwealth University) for Stat1−/− mice; K. Fitzgerald (University of Massachusetts) for the INF-β reporter gene; P. Knapp (Virginia Commonwealth University) for mouse astrocytes; and J. Almenara for tissue processing, sectioning and staining. Supported by the US National Institutes of Health (1R01AI093718 to T.K.; 5R37GM043880 and 1U19AI077435 to S.S.; R01CA160688 to K.T.; 5P30NS047463 to the Virginia Commonwealth University Microscopy Facility; and P30CA16059 to the Massey Cancer Center for support of the Lipidomics Developing Shared Resource and the Flow Cytometry Cores) and the National Natural Science Foundation of China (91029704 to C.L.).",
year = "2014",
month = mar,
doi = "10.1038/ni.2810",
language = "English",
volume = "15",
pages = "231--238",
journal = "Nature immunology",
issn = "1529-2908",
number = "3",
}