TLR-4, IL-1R and TNF-R signaling to NF-kB: variations on a common theme

[en] Toll-like receptors (TLRs) as well as the receptors for tumor necrosis factor (TNF-R) and interleukin-1 (IL-1R) play an important role in innate immunity by regulating the activity of distinct transcription factors such as nuclear factor-kappaB (NF-kappaB). TLR, IL-1R and TNF-R signaling to NF-kappaB converge on a common IkappaB kinase complex that phosphorylates the NF-kappaB inhibitory protein IkappaBalpha. However, upstream signaling components are in large part receptor-specific. Nevertheless, the principles of signaling are similar, involving the recruitment of specific adaptor proteins and the activation of kinase cascades in which protein-protein interactions are controlled by poly-ubiquitination. In this review, we will discuss our current knowledge of NF-kappaB signaling in response to TLR-4, TNF-R and IL-1R stimulation, with a special focus on the similarities and dissimilarities among these pathways.

Research Center/Unit :

Giga-Signal Transduction - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Verstrepen, L.; University of Ghent, VIB

Bekaert, T.; University of Ghent, VIB

Chau, Tieu-Lan ; ULg - Université de Liège

Tavernier, J.; University of Ghent, VIB

Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Beyaert, Rudi; University of Ghent, VIB

Language :

English

Title :

TLR-4, IL-1R and TNF-R signaling to NF-kB: variations on a common theme

Publication date :

2008

Journal title :

Cellular and Molecular Life Sciences

ISSN :

1420-682X

eISSN :

1420-9071

Publisher :

Springer Science & Business Media B.V., Basel, Switzerland

Volume :

Pages :

2964-2978

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 26 November 2008

Statistics

Number of views

784 (11 by ULiège)

Number of downloads

2196 (6 by ULiège)

More statistics

Scopus citations^®

377

Scopus citations^®
without self-citations

373

OpenCitations

323

OpenAlex citations

407

Bibliography

Gilmore, T. D. (2006) Introduction to NF-κB: players, pathways, perspectives. Oncogene 25, 6680-6684.
Hoffman, A., Natoli, G. and Ghosh, G. (2006) Transcriptional regulation via the NF-κB signaling module. Oncogene 25, 6706-6716.
Rothwarf, D. M., Zandi, E., Natoli, G. and Karin, M. (1998) IKKγ is an essential regulatory subunit of the IκB kinase complex. Nature 395, 297-300.
May, M. J., D'Acquisto, F., Madge, L. A., Glöckner, J., Pober, J. S. and Ghosh, S. (2000) Selective inhibition of NF-κB activation by a peptide that blocks the interaction of NEMO with the IκB kinase complex. Science 289, 1550-1554.
Agou, F., Ye, F., Gogginont, S., Courtois, G., Yamaoka, S., Israël, A. and Véron, M. (2002) NEMO trimerizes through its coiled-coil C-terminal domain. J. Biol. Chem. 277, 17464-17475.
Tegethoff, S., Behlke, J. and Scheidereit, C. (2003) Tetrameric oligomerization of IκB kinase γ (IKKγ) is obligatory for IKK complex activity and NF-κB activation. Mol. Cell. Biol. 23, 2029-2041.
Sebban, H., Yamaoka, S. and Courtois, G. (2006) Postranslational modifications of NEMO and its partners in NF-γB signaling. Trends Cell Biol. 16, 569-577.
Wu, C. J., Conze, D. B., Li, T., Srinivasula, S. M. and Ashwell, J. D. (2006) Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation. Nat. Cell. Biol. 8, 398-406.
Brockman, J. A., Scherer, D. C., McKinsey, T. A., Hall, S. M., Qi, X., Lee, W. Y. and Ballard, D. W. (1995) Coupling of a signal response domain in IκBα to multiple pathways for NF-κB activation. Mol. Cell. Biol. 15, 2809-2818.
Brown, K., Gerstberger, S., Carlson, L., Franzoso, G. and Siebenlist, U. (1995) Control of IκB-alpha proteolysis by site-specific, signal-induced phophorylation. Science 267, 1485-1488.
Chen, Z. J. (2005) Ubiquitin signaling in the NF-κB pathway. Nat. Cell Biol. 7, 758-765.
Ducut, S. J. L., Bottero, V., Young, D. B., Shevenko, A., Mercurio, F. and Verma, I. M. (2004) Activation of transcription factor NF-κB requires ELKS, an IκB kinase regulatory subunit. Science 304, 1963-1967.
Dunne, A. and O'Neill, L. A. (2003) The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Science STKE 2003:171, re3.
Haziot, A., Ferrero, E., Kontgen, F., Hijiya, N., Yamamoto, S., Silver, J., Stewart, C. L. and Goyert, S. M. (1996) Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. Immunity 4, 407-414.
Nagai, Y., Akashi, S., Nagafuku, M., Ogata, M., Iwakura, Y., Akira, S., Kitamura, T., Kosugi, A., Kimoto, M. and Miyake, K. (2002) Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat. Immunol. 3, 667-672.
Greenfeder, S. A., Nunes, P., Kwee, L., Labow, M., Chizzonite, R. A. and Ju, G. (1995) Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J. Biol. Chem. 270, 13757-13765.
Huang, J., Goa, X., Li, S. and Cao, Z. (1997) Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein. Proc. Natl. Acad. Sci. USA 94, 12829-12832.
Wesche, H., Henzel, W. J., Sillinglaw, W., Li, S. and Cao, Z. (1997) MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7, 837-847.
Burns, K., Clatworthy, J., Martin, L., Martinon, F., Plumpton, C., Maschera, B., Lewis, A., Ray, K., Tschopp, J. and Volpe, F. (2000) Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat. Cell Biol. 2, 346-351.
Zhang, G. and Ghosh, S. (2002) Negative regulation of Toll-like receptor-mediated signaling by Tollip. J. Biol. Chem. 277, 7059-7065.
Cao, Z., Henzel, W. J. and Gao, X. (1996) IRAK: a kinase associated with the interleukin-1 receptor. Science 271, 1128-1131.
Lamothe, B., Besse, A., Campos, A. D., Webster, W. K., Wu, H. and Darnay, B. G. (2007) Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of IκB kinase activation. J. Biol. Chem. 282, 4102-4112.
Kollewe, C., Mackensen, A. C., Neumann, D., Knop, J., Cao, P., Li, S., Wesche, H. and Martin, M.U. (2004) Sequential autophosphorylation steps in the interkeukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. J. Biol. Chem. 279, 5227-5236.
Ye, H., Arron, J. R., Lamothe, B., Cirilli, M., Kobayashi, T., Shevde, N. K., Segal, D., Dzivenu, O. K., Vologodskaia, M., Yim, M. et al. (2002) Distinct molecular mechanism for initiating TRAF6 signalling. Nature 418, 443-447.
Qin, J., Jiang, Z., Qian, Y., Casanova, J. L. and Li, X. (2004) IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness. J. Biol. Chem. 279, 26748-26753.
Lye, E., Mirtsos, C., Suzuki, N., Suzuki, S. and Yeh, W. C. (2004) The role of interleukin 1 receptor-associated kinase-4 (IRAK-4) kinase activity in IRAK-4-mediated signaling. J. Biol. Chem. 279, 40653-40658.
Jiang, Z., Ninomiya-Tsuji, J., Qian, Y., Matsumoto, K. and Li, X. (2002) Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1and TAB2 at the plasmamembrane and activate TAK1 in the cytosol. Mol. Cell. Biol. 22, 7158-1767.
Cheng, H., Addona, T., Keshishian, H., Dahlstrand, E., Lu, C., Dorsch, M., Li, Z., Wang, A., Ocain, T. D., Li, P. et al. (2006) Regulation of IRAK-4 kinase activity via autophosphorylation within its activation loop. Biochem. Biophys. Res. Commun. 352, 609-616.
Li, X., Commane, M., Burns, C., Vithalani, K., Cao, Z. and Stark, G. R. (1999) Mutant cells that do not respond to interleukin-1 (IL-1) reveal a novel role for IL-1 receptor-associated kinase. Mol. Cell. Biol. 19, 4643-4652.
Yamin, T. T. and Miller, D. K. (1997) The interleukin-1 receptor-associated kinase is degraded by proteasomes following its phosphorylation. J. Biol. Chem. 272, 21540-21547.
Qian, Y., Commane, M., Ninomiya-Tsuji, J., Matsumoto, K. and Li, X. (2001) IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1- induced activation of NF-κB. J. Biol. Chem. 276, 41661-41667.
Windheim, M., Stafford, M., Peggie, M. and Cohen, P. (2008) IL-1 induces the Lys63-linked polyubiquitination of IRAK1 to facilitate NEMO binding and the activation of IKK. Mol. Cell. Biol. Doi:10.1128/MCB.02380-06.
Ordureau, A., Smith, H., Windheim, M., Peggie, M., Carrick, E., Morrice, N. and Cohen, P. (2008) The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1. Biochem., J. 409, 43-52.
Schauvliege, R., Janssens, S. and Beyaert, R. (2006) Pellino proteins are more than scaffold proteins in TLR/IL1-R signalling: a role as novel RING E3-ubiquitin-ligases. FEBS Lett. 580, 4691-4702.
Butler, M. P., Hanly, J. A. and Moynagh, P. N. (2007) Kinase-active interleukin-1 receptor-associated kinases promote polyubiquitination and degradation of the pellino family. J. Biol. Chem. 282, 29729-29737.
Schauvliege, R., Janssens, S. and Beyaert, R. (2007) Pellino proteins: novel players in TLR and IL-1R signalling. J. Cell. Mol. Med. 11, 453-461.
Strelow, A., Kollewe, C. and Wesche, H. (2003) Characterization of Pellino-2, a substrate of IRAK1 and IRAK4. FEBS Lett. 547, 157-161.
Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C. and Chen, Z. J. (2000) Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103, 351-361.
Wang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J. and Chen, Z. J. (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-351.
Wooff, J., Pastushok, L., Hanna, M., Fu, Y. and Xiao, W. (2004) The TRAF6 RING finger domain mediates physical interaction with Ubc13. FEBS Lett. 566, 229-233.
Lomaga, M. A., Yeh, W. C., Sarosi, I., Duncan, G. S., Furlonger, C., Ho, A., Morony, S., Capparelli, C., Van, G., Kaufman, S. et al. (1999) TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev. 13, 1015-1024.
Naito, A., Azuma, S., Tanaka, S., Miyazaki, T., Takaki, S., Takatsu, K., Nakao, K., Nakamura, K., Katsuki, M., Yamamoto, T. et al. (1999) Severe osteopetrosis, defective interleukin-1 singalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 4, 353-362.
Fukushima, T., Matsuzawa, S. I., Kress, C. L., Bruey, J. M., Krajewska, M., Lefebvre, S., Zapata, J. M., Ronai, Z. and Reed, J. C. (2007) Ubiquitin-conjugating enzyme Ubc13 is a critical component of TNF receptor-associated factor (TRAF)-mediated inflammatory responses. Proc. Natl. Acad. Sci. USA 104, 6371-6376.
Yamamoto, M., Okamoto, T., Takeda, K., Sato, S., Sanjo, H., Uematsu, S., Saitoh, T., Yamamoto, N., Sakurai, H., Ishii, K. J. et al. (2006) Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling. Nat. Immunol. 7, 962-970.
Geetha, T., Kenchappa, R. S., Wooten, M. W. and Carter, B. D. (2005) TRAF6-mediated ubiquitination regulates nuclear translocation of NRIF, the p75 receptor interactor. EMBO, J. 24, 3859-3868.
Andersen, P. L., Zhou, H., Pastushok, L., Moraes, T., McKenna, S., Ziola, B., Ellison, M. J., Dixit, V. M. and Xiao, W. (2005) Distinct regulation of Ubc13 functions by the two ubiquitin-conjugating enzyme variants Mms2 and Uev1A. J. Cell Biol. 170, 745-755.
Sun, L., Deng, L., Ea, C. K., Xia, Z. P. and Chen, Z. J. (2004) The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol. Cell 14, 289-301.
Ishitani, T., Takaesu, G., Ninomiya-Tsuji, J., Shibuya, H., Gaynor, R. B. and Matsumoto, K. (2003) Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. EMBOJ. 22, 6277-6288.
Kanayama, A., Seth, R. B., Sun, L., Ea, C. K., Hong, M., Shaito, A., Chiu, Y. H., Deng, L. and Chen, Z. J. (2004) TAB2 and TAB3 activate the NF-κB pathway through binding to polyubiquitin chains. Mol. Cell 15, 535-548.
Ea, C. K., Sun, L., Inoue, J. I. and Chen, Z. J. (2004) TIFA activates IκB kinase (IKK) by promoting oligomerization and ubiquitination of TRAF6. Proc. Natl. Acad. Sci. USA 101, 15318-15323.
Takatsuna, H., Kato, H., Gohda, J., Akiyama, T., Moriya, A., Okamoto, Y., Yamagata, Y., Otsuka, M., Umezawa, K., Semba, K. et al. (2003) Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling. J. Biol. Chem. 278, 12144-12150.
Kanamori, M., Suzuki, H., Saito, R., Muramatsu, M. and Hayashizaki, Y. (2002) T2BP, a novel TRAF2 binding protein, can activate NF-κB and AP-1 without TNF stimulation. Biochem. Biophys. Res. Commun. 290, 1108-1113.
Cheung, P. C. F., Nebreda, A. R. and Cohen, P. (2004) TAB3, a new binding partner of the protein kinase TAK1. Biochem. J. 378, 27-34.
Shim, J. H., Xiao, C., Paschal, A. E., Bailey, S. T., Rao, P., Hayden, M. S., Lee, K. Y., Bussey, C., Steckel, M., Tanaka, N. et al. (2005) TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev. 19, 2668-2681.
Bertelsen, M. and Sanfridson, A. (2007) TAB1 modulates IL-1α mediated cytokine secretion but is dispensable for TAK1 activation. Cell. Signal. 19, 646-657.
Mendoza, H., Campbell, D. G., Burness, K., Hastie, J., Ronkina, N., Shim, J. H., Arthur, J. S. C., Davis, R. J., Gaestel, M., Johnson, G. L. et al. (2008) Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the TAB3 regulatory subunit and activity of the TAK1 complex. Biochem. J. 409, 711-722.
Kishida, S., Sanjo, H., Akira, S., Matsumoto, K. and Ninomiya-Tsuji, J. (2005) TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway. Genes Cells 10, 447-454.
Takaesu, G., Kishida, S., Hiyama, A., Yamaguchi, K., Shibuya, H., Irie, K., Ninomiya-Tsuji, J. and Matsumoto, K. (2000) TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. Mol. Cell 5, 649-658.
Sanjo, H., Takeda, K., Tsujimura, T., Ninomiya-Tsuji, J., Matsumoto, K. and Akira, S. TAB2 is esssential for prevention of apoptosis in fetal liver but not for interleukin-1 signaling. Mol. Cell. Biol. 23, 1231-1238.
Shibuya, H., Yamaguchi, K., Shirakabe, K., Tonegawa, A., Gotoh, Y., Ueno, N., Irie, K., Nishida, E. and Matsumoto, K. (1996) TAB1: an activator of the TAK1 MAPKKK in TGFβ signal transduction. Science 272, 1179-1182.
Takaesu, G., Surabhi, R. M., Park, K. J., Ninomiya-Tsuji, J., Matsumoto, K. and Gaynor, R. B. (2003) TAK1 is critical for IκB kinase-mediated activation of the NF-κB pathway. J. Mol. Biol. 326, 105-115.
Sato, S., Sanjo, H., Takeda, K., Ninomiya-Tsuji, J., Yamamoto, M., Kawai, T., Matsumoto, K., Takeuchi, O., Akira, S., Ninomiya-Tsuji, J. et al. (2005) Essential function for the kinase TAK1 in innate and adaptive immune responses. Nat. Immunol. 6, 1087-1095.
Yao, J., Kim, T.W., Qin, J., Jiang, Z., Qian, Y., Xiao, H., Lu, Y., Qian, W., Gulen, M. F. et al. (2007) Interleukin-1 (IL1)-induced TAK1-dependent versus MEKK3-dependent NFκB activation pathways bifurcate at IL-1 receptor-associated kinase modification. J. Biol. Chem. 282, 6075-6089.
Solt, L. A., Madge, L. A., Orange, J. S. and May, M. J. (2007) Interleukin-1-induced NF-κB activation is NEMO-dependent but does not require IKKβ. J. Biol. Chem. 282, 8724-8733.
Sanz, L., Diaz-Meco, M. T., Nakano, H. and Moscat, J. The atypical PKC-interacting protein p62 channels NF-κB activation by the IL-1-TRAF6 pathway. EMBO J. 19, 1576-1586.
Vadlamudi, R. K., Joung, I., Strominger, J. L. and Shin, J. (1996) p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins. J. Biol. Chem. 271, 20235-20237.
Kopp, E., Medzhitov, R., Carothers, J., Xiao, C., Douglas, I., Janeway, C. A. and Ghosh, S. (1999) ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway. Genes Dev. 13, 2059-2071.
Yamamoto, M., Sato, S., Hemmi, H., Sanjo, H., Uematsu, S., Kaisho, T., Hoshino, K., Takeuchi, O., Kobayashi, M., Fujita, T. et al. (2002) Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 420, 324-328.
Horng, T., Barton, G. M., Flavell, R. A. and Medzhitov, R. (2002) The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420, 329-333.
Kagan, J. C. and Medzhitov, R. (2006) Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell 125, 943-955.
Ulrichts, P., Peelman, F., Beyaert, R. and Tavernier, J. (2007) Mappit analysis of TLR adaptor complexes. FEBS Lett. 581, 629-636.
Gray, P., Dunne, A., Brikos, C., Jefferies, C. A., Doyle, S. L. and O'Neill, L. A. (2006) MyD88 adapter-like (Mal) is phosphorylated by Bruton's tyrosine kinase during TLR2 and TLR4 signal transduction. J. Biol. Chem. 281, 10489-10495.
Kawai, T., Adachi, O., Ogawa, T., Takeda, K. and Akira, S. (1999) Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11, 115-122.
Kawai, T., Takeuchi, O., Fujita, T., Inoue, J., Mühlradt, P. F., Sato, S., Hoshino, K. and Akira, S. (2001) 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. 167, 5887-5894.
Kagan, J. C., Su, T., Horng, T., Chow, A., Akira, S. and Medzhitov, R. (2008) TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat. Immunol. 9, 361-368.
Kawai, T. and Akira, S. (2006) TLR signaling. Cell Death Differ. 13, 816-825.
Gohda, J., Matsumura, T. and Inoue, J. I. (2004) TNFRassociated factor (TRAF) 6 is essential for MyD88-dependent pathway but not Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF)-dependent pathway in TLR signaling. J. Immunol. 173, 2913-2917.
Dong, W., Liu, Y., Peng, J., Chen, L., Zou, T., Xiao, H., Liu, Z., Li, W., Bu, Y. and Qi, Y. (2006) The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-κB from Toll-like receptor 4. J. Biol. Chem. 281, 26029-26040.
Miggin, S. M., Pålsson-McDermott, E., Dunne, A., Jefferies, C., Pinteaux, E., Banahan, K., Murphy, C., Moynagh, P., Yamamoto, M., Akira, S. et al. (2007) NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1. Proc.Natl. Acad. Sci. USA 104, 3372-3377.
Lakshmanan, U. and Porter, A. G. (2007) Caspase-4 interacts with TNF receptor-associated factor 6 and mediates lipopolysaccharide-induced NF-κB-dependent production of IL-8 and CC chemokine ligand 4 (macrophage-inflammatory protein-1b). J. Immunol. 179, 8480-8490.
Aggarwal, B. B. (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat. Rev. Immunol. 3, 745-756.
Micheau, O. and Tschopp, J. (2003) Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114, 181-190.
Harper, N., Hughes, M., MacFarlane, M. and Cohen, G. M. (2003) Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis. J. Biol. Chem. 278, 25534-25541.
Schneider-Brachert, W., Tchikov, V., Neumeyer, J., Jakob, M., Winoto-Morbach, S., Held-Feindt, J., Heinrich, M., Merkel, O., Ehrenschwender, M., Adam, D. et al. (2004) Compartmentalization of TNF receptor 1 signaling: internalized TNF receptosomes as death signaling vesicles. Immunity 21, 415-428.
Hsu, H., Shu, H. B., Pan, M. G. and Goeddel, D.V. (1996) TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84, 299-308.
Hsu, H., Huang, J., Shu, H. B., Baichwal, V. and Goeddel, D.V. (1996) TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity 4, 387-396.
Tada, K., Okazaki, T., Sakon, S., Kobarai, T., Kurosawa, K., Yamaoka, S., Hashimoto, H., Mak, T.W., Yagita, H., Okumura, K. et al. (2001) Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-κB activation and protection from cell death. J. Biol. Chem. 276, 36530-36534.
Yeh, W. C., Shahinian, A., Speiser, D., Kraunus, J., Billia, F., Wakeham, A., de la Pompa, J. L., Ferrick, D., Hum, B., Iscove, N. et al. (1997) Early lethality, functional NF-κB activation and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity 7, 715-725.
Habelhah, H., Takahashi, S., Cho, S. G., Kadoya, T., Watanabe, T. and Ronai, Z. (2004) Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-κB. EMBO J. 23, 322-332.
Shi, C. S. and Kehrl, J. H. (2003) Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and stress-activated protein kinase (SAPK) activation depends upon the E2/E3 complex Ubc13-Uev1Q/TNF receptor-associated factor 2 (TRAF2). J. Biol. Chem. 278, 15429-15434.
Dadgostar, H. and Cheng, G. (1998) An intact zinc ring finger is required for tumor necrosis factor receptor-associated factor-mediated nuclear factor-κB activation but is dispensable for c-Jun N-terminal kinase signaling. J. Biol. Chem. 273, 24775- 24780.
Devin, A., Cook, A., Lin, Y., Rodriguez, Y., Kelliher, M. and Liu, Z. (2000) The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1while RIP mediates IKK activation. Immunity 12, 419-429.
Lee, T. H., Shank, J., Cusson, N. and Kelliher, M. A. (2004) The kinase activity of RIP1 is not required for tumor necrosis factor-α-induced IκB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2. J. Biol. Chem. 279, 33185-33191.
Legler, D. F., Micheau, O., Doucey, M. A., Tschopp, J. and Bron, C. (2003) Recruitment of TNFreceptor 1 to lipid rafts is essential for TNFα-mediated NF-κB activation. Immunity 18, 655-664.
Kelliher, M. A., Grimm, S., Ishida, Y., Kuo, F., Stanger, B.Z. and Leder, P. (1998) The death domain kinase RIP mediates the TNF-induced NF-κB signal. Immunity 8, 297-303.
Blonska, M., Shambharkar, P. B., Kobayashi, M., Zhang, D., Sakurai, H., Su, B. and Lin, X. (2005) TAK1 is recruited to the tumor necrosis factor-α (TNF-α) receptor 1 complex in a receptor-interacting protein (RIP)-dependent manner and cooperates with MEKK3 leading to NF-κB activation. J. Biol. Chem. 280, 43056-43063.
Ea, C. K., Deng, L., Xia, Z. P., Pineda, G. and Chen, Z. J. (2006) Activation of IKK by TNFα requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol. Cell 22, 245-257.
Li, H., Kobayashi, M., Blonska, M., You, Y. and Lin, X. (2006) Ubiquitination of RIP is required for tumor necrosis factor α-induced NF-κB activation. J. Biol. Chem. 281, 13636-13643.
Zhang, S. Q., Kovalenko, A., Cantarella, G. and Wallach, D. (2000) Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKγ) upon receptor stimulation. Immunity 12, 301-311.
Wertz, I. E., O'Rourke, K. M., Zhou, H., Eby, M., Aravind, L., Seshagiri, S., Wu, P., Wiesmann, C., Baker, R., Boone, D. L. et al. (2004) De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signaling. Nature 430, 694-699.
Yang, J., Lin, Y., Guo, Z., Cheng, J., Huang, J., Deng, L., Liao, W., Chen, Z., Liu, Z. and Su, B. (2001) The essential role of MEKK3 in TNF-induced NF-κB activation. Nat. Immunol. 2, 620-624.
Blonska, M., You, Y., Geleziunas, R. and Lin, X. (2004) Restoration of NF-κB activation by tumor necrosis factor alpha receptor complex-targeted MEKK3 in receptor-interacting protein-deficient cells. Mol. Cell. Biol. 24, 10757-10765.
Di, Y., Li, S., Wang, L., Zhang, Y. and Dorf, M. E. (2008) Homeostatic interactions beween MEKK3 and TAK1 involved in NF-κB signaling. Cell. Signal. 20, 705-713.
Sanz, L., Sanchez, P., Lallena, M. J., Diaz-Meco, M. T. and Moscat, J. (1999) The interaction of p62 with RIP links the atypical PKCs to NF-κB activation. EMBO J. 18, 3044-3053.
Meylan, E., Martinon, F., Thome, M., Gschwendt, M. and Tschopp, J. (2002) RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF-κB and is processed during apoptosis. EMBO Rep. 3, 1201-1208.
Festjens, N., Vandenberghe, T., Cornelis, S. and Vandenabeele, P. (2007) RIP1, a kinase on the crossroads of a cell's decision to live or die. Cell Death Differ. 14, 400-410.
Heyninck, K. and Beyaert, R. (2005) A20 inhibits NF-κB activation by dual ubiquitin-editing functions. Trends Biochem. Sci. 30, 1-4.
Burns, K., Janssens, S., Brissoni, B., Olivos, N., Beyaert, R. and Tschopp, J. (2003) Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced short form of MyD88 is due to its failure to recruit IRAK4. J. Exp. Med. 197, 263-268.
Janssens, S., Burns, K., Tschopp, J. and Beyaert, R. (2002) Regulation of interleukin-1- and lipopolysaccharide-induced NF-κB activation by alternative splicing of MyD88. Curr. Biol. 12, 467-471.
Iha, H., Peloponese, J. M., Verstrepen, L., Zapart, G., Ikeda, F., Smith, C. D., Starost, M. F., Yedavalli, V., Heyninck, K., Dikic, I. et al. (2008) Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-κB activation. EMBO J. 27, 629-641.
Shembade, N., Harhaj, N. S., Liebl, D. J. and Harhaj, E.W. (2007) Essential role for TAX1BP1 in the termination of TNF-α-, IL-1- and LPS-mediated NF-κB and JNK signaling. EMBO J. 26, 3910-3922.
Kuek, A., Hazleman, B. L. and Ostör, A. J. (2007) Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad. Med. J. 83, 251-260.
Romagne, F. (2007) Current and future drugs targeting one class of innate immunity receptors: the Toll-like receptors. Drug Discov. Today 12, 80-87.