K63-linked polyubiquitination of transcription factor IRF1 is essential for IL-1-induced production of chemokines CXCL10 and CCL5

被引：107

作者：

Harikumar, Kuzhuvelil B. ^{[1
,2
]}

Yester, Jessie W. ^{[1
,2
]}

Surace, Michael J. ^{[1
,2
]}

Oyeniran, Clement ^{[1
,2
]}

Price, Megan M. ^{[1
,2
]}

Huang, Wei-Ching ^{[1
,2
]}

Hait, Nitai C. ^{[1
,2
]}

Allegood, Jeremy C. ^{[1
,2
]}

Yamada, Akimitsu ^{[1
,2
,3
]}

Kong, Xiangqian ^{[4
]}

Lazear, Helen M. ^{[5
,6
]}

Bhardwaj, Reetika ^{[1
,2
]}

Takabe, Kazuaki ^{[1
,2
,3
]}

Diamond, Michael S. ^{[5
,6
]}

Luo, Cheng ^{[4
]}

Milstien, Sheldon ^{[1
,2
]}

Spiegel, Sarah ^{[1
,2
]}

Kordula, Tomasz ^{[1
,2
]}

机构：

[1] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Sch Med, Richmond, VA 23284 USA

[2] Virginia Commonwealth Univ, Massey Canc Ctr, Sch Med, Richmond, VA USA

[3] Virginia Commonwealth Univ, Dept Surg, Sch Med, Richmond, VA USA

[4] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China

[5] Washington Univ, Sch Med, Dept Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[6] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 03期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

NF-KAPPA-B; REGULATORY FACTOR-I; SYNERGISTIC ACTIVATION; EXPRESSION; KINASE; IL-1; SPHINGOSINE-1-PHOSPHATE; LIPOPOLYSACCHARIDE; UBIQUITINATION; INHIBITOR;

D O I：

10.1038/ni.2810

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 SIP. 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.

引用

页码：231 / 238

页数：8

共 44 条

[1] Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2 [J].