K63-linked Polyubiquitination of Transcription Factor IRF1 is Essential for IL-1-induced Production of Chemokines CXCL10 and CCL5

Overview

Journal Nat Immunol

Date 2014 Jan 28

PMID 24464131

Citations 74

Authors

Kuzhuvelil B Harikumar

Jessie W Yester

Michael J Surace

Clement Oyeniran

Megan M Price

Wei-Ching Huang

Nitai C Hait

Jeremy C Allegood

Akimitsu Yamada

Xiangqian Kong

Helen M Lazear

Reetika Bhardwaj

Kazuaki Takabe

Michael S Diamond

Cheng Luo

Sheldon Milstien

Sarah Spiegel

Tomasz Kordula

Affiliations

Soon will be listed here.

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.

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References

Chen Z . Ubiquitin signalling in the NF-kappaB pathway. Nat Cell Biol. 2005; 7(8):758-65. PMC: 1551980. DOI: 10.1038/ncb0805-758. View

Ning S, Campos A, Darnay B, Bentz G, Pagano J . TRAF6 and the three C-terminal lysine sites on IRF7 are required for its ubiquitination-mediated activation by the tumor necrosis factor receptor family member latent membrane protein 1. Mol Cell Biol. 2008; 28(20):6536-46. PMC: 2577435. DOI: 10.1128/MCB.00785-08. View

Pitson S, Moretti P, Zebol J, Lynn H, Xia P, Vadas M . Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation. EMBO J. 2003; 22(20):5491-500. PMC: 213794. DOI: 10.1093/emboj/cdg540. View

Venkatesh D, Ernandez T, Rosetti F, Batal I, Cullere X, Luscinskas F . Endothelial TNF receptor 2 induces IRF1 transcription factor-dependent interferon-β autocrine signaling to promote monocyte recruitment. Immunity. 2013; 38(5):1025-37. PMC: 3760474. DOI: 10.1016/j.immuni.2013.01.012. View

ONeill L . The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev. 2009; 226:10-8. DOI: 10.1111/j.1600-065X.2008.00701.x. View

Kawai T, Takeuchi O, Fujita T, Inoue J, Muhlradt P, Sato S . Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol. 2001; 167(10):5887-94. DOI: 10.4049/jimmunol.167.10.5887. View

Hinz M, Stilmann M, Arslan S, Khanna K, Dittmar G, Scheidereit C . A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-κB activation. Mol Cell. 2010; 40(1):63-74. DOI: 10.1016/j.molcel.2010.09.008. View

Reis L, Ruffner H, Stark G, Aguet M, Weissmann C . Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes. EMBO J. 1994; 13(20):4798-806. PMC: 395418. DOI: 10.1002/j.1460-2075.1994.tb06805.x. View

Petersen S, Wang L, Yalcin-Chin A, Li L, Peyton M, Minna J . Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell. 2007; 12(5):445-56. PMC: 3431210. DOI: 10.1016/j.ccr.2007.08.029. View

10.

Deng L, Wang C, Spencer E, Yang L, Braun A, You J . Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000; 103(2):351-61. DOI: 10.1016/s0092-8674(00)00126-4. View

11.

Kordula T, Rydel R, Brigham E, Horn F, Heinrich P, Travis J . Oncostatin M and the interleukin-6 and soluble interleukin-6 receptor complex regulate alpha1-antichymotrypsin expression in human cortical astrocytes. J Biol Chem. 1998; 273(7):4112-8. DOI: 10.1074/jbc.273.7.4112. View

12.

Zarnegar B, Wang Y, Mahoney D, Dempsey P, Cheung H, He J . Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat Immunol. 2008; 9(12):1371-8. PMC: 2676931. DOI: 10.1038/ni.1676. View

13.

Zheng C, Kabaleeswaran V, Wang Y, Cheng G, Wu H . Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation. Mol Cell. 2010; 38(1):101-13. PMC: 2855162. DOI: 10.1016/j.molcel.2010.03.009. View

14.

Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel D . TRAF6 is a signal transducer for interleukin-1. Nature. 1996; 383(6599):443-6. DOI: 10.1038/383443a0. View

15.

Janssens S, Beyaert R . A universal role for MyD88 in TLR/IL-1R-mediated signaling. Trends Biochem Sci. 2002; 27(9):474-82. DOI: 10.1016/s0968-0004(02)02145-x. View

16.

Lin R, Heylbroeck C, Genin P, Pitha P, Hiscott J . Essential role of interferon regulatory factor 3 in direct activation of RANTES chemokine transcription. Mol Cell Biol. 1999; 19(2):959-66. PMC: 116027. DOI: 10.1128/MCB.19.2.959. View

17.

Conze D, Wu C, Thomas J, Landstrom A, Ashwell J . Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation. Mol Cell Biol. 2008; 28(10):3538-47. PMC: 2423148. DOI: 10.1128/MCB.02098-07. View

18.

Arend W . The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev. 2002; 13(4-5):323-40. DOI: 10.1016/s1359-6101(02)00020-5. View

19.

Shultz D, Rani M, Fuller J, Ransohoff R, Stark G . Roles of IKK-beta, IRF1, and p65 in the activation of chemokine genes by interferon-gamma. J Interferon Cytokine Res. 2009; 29(12):817-24. PMC: 2956658. DOI: 10.1089/jir.2009.0034. View

20.

Tada Y, Ho A, Matsuyama T, Mak T . Reduced incidence and severity of antigen-induced autoimmune diseases in mice lacking interferon regulatory factor-1. J Exp Med. 1997; 185(2):231-8. PMC: 2196116. DOI: 10.1084/jem.185.2.231. View