Peli1 facilitates TRIF-dependent Toll-like receptor signaling and proinflammatory cytokine production

被引：214

作者：

Chang, Mikyoung ^{[1
]}

Jin, Wei ^{[1
]}

Sun, Shao-Cong ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 10期

基金：

美国国家卫生研究院;

关键词：

NF-KAPPA-B; NECROSIS-FACTOR RECEPTOR; DOMAIN-CONTAINING ADAPTER; TUMOR-SUPPRESSOR CYLD; PELLINO PROTEINS; INFLAMMATORY RESPONSES; REGULATORY FACTOR-3; IMMUNE-RESPONSES; CUTTING EDGE; ACTIVATION;

D O I：

10.1038/ni.1777

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Toll-like receptors (TLRs) are pivotal in innate immunity and inflammation. Here we show that genetic deficiency in Peli1, an E3 ubiquitin ligase, attenuated the induction of proinflammatory cytokines by ligands of TLR3 and TLR4 and rendered mice resistant to septic shock. Peli1 was required for TLR3-induced activation of I. B kinase (IKK) and its 'downstream' target, transcription factor NF-kappa B, but was dispensable for IKK-NF-kappa B activation induced by several other TLRs and the interleukin 1 (IL-1) receptor. Notably, Peli1 bound to and ubiquitinated RIP1, a signaling molecule that mediates IKK activation induced by the TLR3 and TLR4 adaptor TRIF. Our findings suggest that Peli1 is a ubiquitin ligase needed for the transmission of TRIF-dependent TLR signals.

引用

页码：1089 / U66

页数：8

共 49 条

[1] Ubiquitin-mediated activation of TAK1 and IKK [J].

Adhikari, A. ;

Xu, M. ;

Chen, Z. J. .

ONCOGENE, 2007, 26 (22) :3214-3226

[2] Pathogen recognition and innate immunity [J].

Akira, S ;

Uematsu, S ;

Takeuchi, O .

CELL, 2006, 124 (04) :783-801

[3] Kinase-active interleukin-1 receptor-associated kinases promote polyubiquitination and degradation of the Pellino family - Direct evidence for pellino proteins being ubiquitin-protein isopeptide ligases [J].

Butler, Marion P. ;

Hanly, Jennifer A. ;

Moynagh, Paul N. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (41) :29729-29737

[4] Beyond tumor necrosis factor receptor:: TRADD signaling in toll-like receptors [J].

Chen, Nien-Jung ;

Chio, Iok In Christine ;

Lin, Wen-Jye ;

Duncan, Gordon ;

Chau, Hien ;

Katz, David ;

Huang, Huey-Lan ;

Pike, Kelly A. ;

Hao, Zhenyue ;

Su, Yu-Wen ;

Yamamoto, Kazuo ;

de Pooter, Renee F. ;

Zuniga-Pflucker, Juan Carlos ;

Wakeham, Andrew ;

Yeh, Wen-Chen ;

Mak, Tak W. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (34) :12429-12434

[5] Rip1 mediates the Trif-dependent Toll-like receptor 3- and 4-induced NF-κB activation but does not contribute to interferon regulatory factor 3 activation [J].

Cusson-Hermance, N ;

Khurana, S ;

Lee, TH ;

Fitzgerald, KA ;

Kelliher, MA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (44) :36560-36566

[6] Tumor necrosis factor alpha mediates the lethal hepatotoxic effects of poly(I:C) in D-galactosamine-sensitized mice [J].

Dejager, Lien ;

Libert, Claude .

CYTOKINE, 2008, 42 (01) :55-61

[7] Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses [J].

Ermolaeva, Maria A. ;

Michallet, Marie-Cecile ;

Papadopoulou, Nikoletta ;

Utermoehlen, Olaf ;

Kranidioti, Ksanthi ;

Kollias, George ;

Tschopp, Juerg ;

Pasparakis, Manolis .

NATURE IMMUNOLOGY, 2008, 9 (09) :1037-1046

[8] IKKε and TBK1 are essential components of the IRF3 signaling pathway [J].

Fitzgerald, KA ;

McWhirter, SM ;

Faia, KL ;

Rowe, DC ;

Latz, E ;

Golenbock, DT ;

Coyle, AJ ;

Liao, SM ;

Maniatis, T .

NATURE IMMUNOLOGY, 2003, 4 (05) :491-496

[9] GALACTOSAMINE-INDUCED SENSITIZATION TO THE LETHAL EFFECTS OF ENDOTOXIN [J].

GALANOS, C ;

FREUDENBERG, MA ;

REUTTER, W .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1979, 76 (11) :5939-5943

[10] Regulating B-cell activation and survival in response to TLR signals [J].

Gerondakis, Steve ;

Grumont, Raelene J. ;

Banerjee, Ashish .

IMMUNOLOGY AND CELL BIOLOGY, 2007, 85 (06) :471-475

← 1 2 3 4 5 →