No one can whistle a symphony alone - how different ubiquitin linkages cooperate to orchestrate NF-κb activity

Journal of Cell Science

Volumn 125, Issue 3, 2012, Pages 549-559

  Schmukle, Anna C ^a   Walczak, Henning ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DEUBIQUITYLATING ENZYME; ENZYME; I KAPPA B ALPHA; I KAPPA B KINASE GAMMA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PROTEIN P100; RECEPTOR INTERACTING PROTEIN 140; TRANSCRIPTION FACTOR REL; TRANSFORMING GROWTH FACTOR BETA ACTIVATED KINASE 1; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 2; UNCLASSIFIED DRUG;

ARTICLE; CYLINDROMA; DNA BINDING; ENZYME ACTIVATION; GENETIC LINKAGE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STABILITY; SIGNAL TRANSDUCTION; UBIQUITINATION;

I-KAPPA B PROTEINS; LYSINE; MODELS, BIOLOGICAL; NF-KAPPA B; PHOSPHORYLATION; RECEPTORS, TUMOR NECROSIS FACTOR, TYPE I; SIGNAL TRANSDUCTION; UBIQUITIN; UBIQUITINATION;

EID: 84858113865     PISSN: 00219533     EISSN: 14779137     Source Type: Journal    
DOI: 10.1242/jcs.091793     Document Type: Article

References (138)

1. Abbott, D. W., Yang, Y., Hutti, J. E., Madhavarapu, S., Kelliher, M. A. and Cantley, L. C. (2007). Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains. Mol. Cell. Biol. 27, 6012-6025.
2. Ahmed, A. U., Moulin, M., Coumailleau, F., Wong, W. W., Miasari, M., Carter, H., Silke, J., Cohen-Tannoudji, M., Vince, J. E. and Vaux, D. L. (2009). CARP2 deficiency does not alter induction of NF-kappaB by TNFalpha. Curr. Biol. 19, R15-R19.
3. Alvarez, S. E., Harikumar, K. B., Hait, N. C., Allegood, J., Strub, G. M., Kim, E. Y., Maceyka, M., Jiang, H., Luo, C., Kordula, T. et al. (2010). Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature 465, 1084-1088.
4. Arimoto, K., Takahashi, H., Hishiki, T., Konishi, H., Fujita, T. and Shimotohno, K. (2007). Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc. Natl. Acad. Sci. USA 104, 7500-7505.
5. Arimoto, K., Funami, K., Saeki, Y., Tanaka, K., Okawa, K., Takeuchi, O., Akira, S., Murakami, Y. and Shimotohno, K. (2010). Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense. Proc. Natl. Acad. Sci. USA 107, 15856-15861.
6. Baltimore, D. (2011). NF-kappaB is 25. Nat. Immunol. 12, 683-685.
7. Behrends, C. and Harper, J. W. (2011). Constructing and decoding unconventional ubiquitin chains. Nat. Struct. Mol. Biol. 18, 520-528.
8. Ben-Neriah, Y. and Karin, M. (2011). Inflammation meets cancer, with NF-kappaB as the matchmaker. Nat. Immunol. 12, 715-723.
9. Bertrand, M. J., Milutinovic, S., Dickson, K. M., Ho, W. C., Boudreault, A., Durkin, J., Gillard, J. W., Jaquith, J. B., Morris, S. J. and Barker, P. A. (2008). cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol. Cell 30, 689-700.
10. Bertrand, M. J., Doiron, K., Labbe, K., Korneluk, R. G., Barker, P. A. and Saleh, M. (2009). Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2. Immunity 30, 789-801.
11. Bloor, S., Ryzhakov, G., Wagner, S., Butler, P. J., Smith, D. L., Krumbach, R., Dikic, I. and Randow, F. (2008). Signal processing by its coil zipper domain activates IKK gamma. Proc. Natl. Acad. Sci. USA 105, 1279-1284.
12. Bremm, A., Freund, S. M. and Komander, D. (2010). Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne. Nat. Struct. Mol. Biol. 17, 939-947.
13. Brummelkamp, T. R., Nijman, S. M., Dirac, A. M. and Bernards, R. (2003). Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature 424, 797-801.
14. Chau, V., Tobias, J. W., Bachmair, A., Marriott, D., Ecker, D. J., Gonda, D. K. and Varshavsky, A. (1989). A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243, 1576-1583.
15. Chen, Z. J. and Sun, L. J. (2009). Nonproteolytic functions of ubiquitin in cell signaling. Mol. Cell 33, 275-286.
16. Cheung, P. C., Nebreda, A. R. and Cohen, P. (2004). TAB3, a new binding partner of the protein kinase TAK1. Biochem. J. 378, 27-34.
17. Conze, D. B., Wu, C. J., Thomas, J. A., Landstrom, A. and Ashwell, J. D. (2008). Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation. Mol. Cell. Biol. 28, 3538-3547.
18. Courtois, G. and Gilmore, T. D. (2006). Mutations in the NF-kappaB signaling pathway: implications for human disease. Oncogene 25, 6831-6843.
19. Courtois, G. and Israel, A. (2011). IKK regulation and human genetics. Curr. Top. Microbiol. Immunol. 349, 73-95.
20. Damgaard, R. B. and Gyrd-Hansen, M. (2011). Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity. Discov. Med. 11, 221-231.
21. Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C. and Chen, Z. J. (2000). Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103, 351-361.
22. Derudder, E., Dejardin, E., Pritchard, L. L., Green, D. R., Korner, M. and Baud, V. (2003). RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100. J. Biol. Chem. 278, 23278-23284.
23. Dikic, I. and Dotsch, V. (2009). Ubiquitin linkages make a difference. Nat. Struct. Mol. Biol. 16, 1209-10.
24. Dynek, J. N., Goncharov, T., Dueber, E. C., Fedorova, A. V., Izrael-Tomasevic, A., Phu, L., Helgason, E., Fairbrother, W. J., Deshayes, K., Kirkpatrick, D. S. et al. (2010). c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J. 29, 4198-4209.
25. Ea, C. K., Deng, L., Xia, Z. P., Pineda, G. and Chen, Z. J. (2006). Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol. Cell 22, 245-257.
26. Emmerich, C. H., Schmukle, A. C. and Walczak, H. (2011). The emerging role of linear ubiquitination in cell signaling. Sci. Signal. 4, re5.
27. Fan, Y., Yu, Y., Shi, Y., Sun, W., Xie, M., Ge, N., Mao, R., Chang, A., Xu, G., Schneider, M. D. et al. (2010). Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor necrosis factor alpha- and interleukin-1beta-induced IKK/NFkappaB and JNK/AP-1 activation. J. Biol. Chem. 285, 5347-5360.
28. Fearns, C., Pan, Q., Mathison, J. C. and Chuang, T. H. (2006). Triad3A regulates ubiquitination and proteasomal degradation of RIP1 following disruption of Hsp90 binding. J. Biol. Chem. 281, 34592-34600.
29. Fushman, D. and Walker, O. (2010). Exploring the linkage dependence of polyubiquitin conformations using molecular modeling. J. Mol. Biol. 395, 803-814.
30. Gack, M. U., Shin, Y. C., Joo, C. H., Urano, T., Liang, C., Sun, L., Takeuchi, O., Akira, S., Chen, Z., Inoue, S. et al. (2007). TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446, 916-920.
31. Gautheron, J. and Courtois, G. (2010). "Without Ub I am nothing" NEMO as a multifunctional player in ubiquitin-mediated control of NF-kappaB activation. Cell Mol. Life Sci. 67, 3101-3113.
32. Gerlach, B., Cordier, S. M., Schmukle, A. C., Emmerich, C. H., Rieser, E., Haas, T. L., Webb, A. I., Rickard, J. A., Anderton, H., Wong, W. W. et al. (2011). Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 471, 591-596.
33. Haas, T. L., Emmerich, C. H., Gerlach, B., Schmukle, A. C., Cordier, S. M., Rieser, E., Feltham, R., Vince, J., Warnken, U., Wenger, T. et al. (2009). Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol. Cell 36, 831-844.
34. Hadian, K. and Krappmann, D. (2011). Signals from the nucleus: activation of NFkappaB by cytosolic ATM in the DNA damage response. Sci. Signal. 4, pe2.
35. Hadian, K., Griesbach, R. A., Dornauer, S., Wanger, T. M., Nagel, D., Metlitzky, M., Beisker, W., Schmidt-Supprian, M. and Krappmann, D. (2011). NF-{kappa}B Essential Modulator (NEMO) Interaction with Linear and Lys-63 Ubiquitin Chains Contributes to NF-{kappa}B Activation. J. Biol. Chem. 286, 26107-26117.
36. Harhaj, E. W. and Dixit, V. M. (2011). Deubiquitinases in the regulation of NF-kappaB signaling. Cell Res. 21, 22-39.
37. Hasegawa, M., Fujimoto, Y., Lucas, P. C., Nakano, H., Fukase, K., Nunez, G. and Inohara, N. (2008). A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. EMBO J. 27, 373-383.
38. Hayden, M. S. and Ghosh, S. (2008). Shared principles in NF-kappaB signaling. Cell 132, 344-362.
39. Heyninck, K., De Valck, D., Vanden Berghe, W., Van Criekinge, W., Contreras, R., Fiers, W., Haegeman, G. and Beyaert, R. (1999). The zinc finger protein A20 inhibits TNF-induced NF-kappaB-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal and directly binds to a novel NF-kappaBinhibiting protein ABIN. J. Cell Biol. 145, 1471-1482.
40. Hinz, M., Stilmann, M., Arslan, S. C., Khanna, K. K., Dittmar, G. and Scheidereit, C. (2010). A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-kappaB activation. Mol. Cell 40, 63-74.
41. Hochstrasser, M. (2006). Lingering mysteries of ubiquitin-chain assembly. Cell 124, 27-34.
42. Hoeller, D., Crosetto, N., Blagoev, B., Raiborg, C., Tikkanen, R., Wagner, S., Kowanetz, K., Breitling, R., Mann, M., Stenmark, H. et al. (2006). Regulation of ubiquitinbinding proteins by monoubiquitination. Nat. Cell Biol. 8, 163-169.
43. Hofmann, R. M. and Pickart, C. M. (1999). Noncanonical MMS2-encoded ubiquitinconjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96, 645-653.
44. Hoffmann, A. and Baltimore, D. (2006). Circuitry of nuclear factor kappaB signaling. Immunol. Rev. 210, 171-186.
45. Huang, H., Jeon, M. S., Liao, L., Yang, C., Elly, C., Yates, J. R., 3rd. and Liu, Y. C. (2010). K33-linked polyubiquitination of T cell receptor-zeta regulates proteolysisindependent T cell signaling. Immunity 33, 60-70.
46. Ikeda, F., Deribe, Y. L., Skanland, S. S., Stieglitz, B., Grabbe, C., Franz-Wachtel, M., van Wijk, S. J., Goswami, P., Nagy, V., Terzic, J. et al. (2011). SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis. Nature 471, 637-641.
47. Inn, K. S., Gack, M. U., Tokunaga, F., Shi, M., Wong, L. Y., Iwai, K. and Jung, J. U. (2011). Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction. Mol. Cell 41, 354-365.
48. Jaattela, M., Mouritzen, H., Elling, F. and Bastholm, L. (1996). A20 zinc finger protein inhibits TNF and IL-1 signaling. J. Immunol. 156, 1166-1173.
49. Kanarek, N., London, N., Schueler-Furman, O. and Ben-Neriah, Y. (2010). Ubiquitination and degradation of the inhibitors of NF-kappaB. Cold Spring Harb. Perspect Biol. 2, a000166.
50. 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-kappaB pathway through binding to polyubiquitin chains. Mol. Cell 15, 535-548.
51. Karin, M. and Ben-Neriah, Y. (2000). Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu. Rev. Immunol. 18, 621-663.
52. Kirisako, T., Kamei, K., Murata, S., Kato, M., Fukumoto, H., Kanie, M., Sano, S., Tokunaga, F., Tanaka, K. and Iwai, K. (2006). A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 25, 4877-4887.
53. Kirkin, V. and Dikic, I. (2011). Ubiquitin networks in cancer. Curr. Opin. Genet. Dev. 21, 21-28.
54. 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.
55. Komander, D. (2009). The emerging complexity of protein ubiquitination. Biochem. Soc. Trans. 37, 937-953.
56. Komander, D. (2010). Mechanism, specificity and structure of the deubiquitinases. Subcell Biochem. 54, 69-87.
57. Komander, D. and Barford, D. (2008). Structure of the A20 OTU domain and mechanistic insights into deubiquitination. Biochem. J. 409, 77-85.
58. Komander, D., Lord, C. J., Scheel, H., Swift, S., Hofmann, K., Ashworth, A. and Barford, D. (2008). The structure of the CYLD USP domain explains its specificity for Lys63-linked polyubiquitin and reveals a B box module. Mol. Cell 29, 451-464.
59. Komander, D., Clague, M. J. and Urbe, S. (2009a). Breaking the chains: structure and function of the deubiquitinases. Nat. Rev. Mol. Cell. Biol. 10, 550-563.
60. Komander, D., Reyes-Turcu, F., Licchesi, J. D., Odenwaelder, P., Wilkinson, K. D. and Barford, D. (2009b). Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Rep. 10, 466-473.
61. Kovalenko, A., Chable-Bessia, C., Cantarella, G., Israel, A., Wallach, D. and Courtois, G. (2003). The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature 424, 801-805.
62. Kulathu, Y., Akutsu, M., Bremm, A., Hofmann, K. and Komander, D. (2009). Twosided ubiquitin binding explains specificity of the TAB2 NZF domain. Nat. Struct. Mol. Biol. 16, 1328-1330.
63. Laplantine, E., Fontan, E., Chiaravalli, J., Lopez, T., Lakisic, G., Veron, M., Agou, F. and Israel, A. (2009). NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain. EMBO J. 28, 2885-2895.
64. Lee, T. H., Shank, J., Cusson, N. and Kelliher, M. A. (2004). The kinase activity of Rip1 is not required for tumor necrosis factor-alpha-induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2. J. Biol. Chem. 279, 33185-33191.
65. Li, H., Kobayashi, M., Blonska, M., You, Y. and Lin, X. (2006). Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation. J. Biol. Chem. 281, 13636-13643.
66. Li, S., Wang, L. and Dorf, M. E. (2009). PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63-linked polyubiquitination. Mol. Cell 33, 30-42.
67. Liao, G., Zhang, M., Harhaj, E. W. and Sun, S. C. (2004). Regulation of the NFkappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J. Biol. Chem. 279, 26243-26250.
68. Liao, W., Xiao, Q., Tchikov, V., Fujita, K., Yang, W., Wincovitch, S., Garfield, S., Conze, D., El-Deiry, W. S., Schutze, S. et al. (2008). CARP-2 is an endosomeassociated ubiquitin ligase for RIP and regulates TNF-induced NF-kappaB activation. Curr. Biol. 18, 641-649.
69. Liu, S. and Chen, Z. J. (2011). Expanding role of ubiquitination in NF-kappaB signaling. Cell Res. 21, 6-21.
70. Lo, Y. C., Lin, S. C., Rospigliosi, C. C., Conze, D. B., Wu, C. J., Ashwell, J. D., Eliezer, D. and Wu, H. (2009). Structural basis for recognition of diubiquitins by NEMO. Mol. Cell 33, 602-615.
71. Matsumoto, M. L., Wickliffe, K. E., Dong, K. C., Yu, C., Bosanac, I., Bustos, D., Phu, L., Kirkpatrick, D. S., Hymowitz, S. G., Rape, M. et al. (2010). K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody. Mol. Cell 39, 477-484.
72. Matsuzawa, A., Tseng, P. H., Vallabhapurapu, S., Luo, J. L., Zhang, W., Wang, H., Vignali, D. A., Gallagher, E. and Karin, M. (2008). Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science 321, 663-668.
73. Mauro, C., Pacifico, F., Lavorgna, A., Mellone, S., Iannetti, A., Acquaviva, R., Formisano, S., Vito, P. and Leonardi, A. (2006). ABIN-1 binds to NEMO/IKKgamma and co-operates with A20 in inhibiting NF-kappaB. J. Biol. Chem. 281, 18482-18488.
74. Miyamoto, S. (2011). Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage. Cell Res. 21, 116-130.
75. Moynagh, P. N. (2009). The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling. Trends Immunol. 30, 33-42.
76. Newton, K., Matsumoto, M. L., Wertz, I. E., Kirkpatrick, D. S., Lill, J. R., Tan, J., Dugger, D., Gordon, N., Sidhu, S. S., Fellouse, F. A. et al. (2008). Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies. Cell 134, 668-678.
77. Niu, J., Shi, Y., Iwai, K. and Wu, Z. H. (2011). LUBAC regulates NF-kappaB activation upon genotoxic stress by promoting linear ubiquitination of NEMO. EMBO J. 30, 3741-3753.
78. O'Dea, E. and Hoffmann, A. (2009). NF-kappaB signaling. Wiley Interdiscip. Rev. Syst. Biol. Med. 1, 107-115.
79. Oeckinghaus, A. and Ghosh, S. (2009). The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol. 1, a000034.
80. Oeckinghaus, A., Wegener, E., Welteke, V., Ferch, U., Arslan, S. C., Ruland, J., Scheidereit, C. and Krappmann, D. (2007). Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. EMBO J. 26, 4634-4645.
81. 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.
82. Oshiumi, H., Matsumoto, M., Hatakeyama, S. and Seya, T. (2009). Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection. J. Biol. Chem. 284, 807-817.
83. Park, S. M., Yoon, J. B. and Lee, T. H. (2004). Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) in vitro. FEBS Lett. 566, 151-156.
84. Passmore, L. A. and Barford, D. (2004). Getting into position: the catalytic mechanisms of protein ubiquitylation. Biochem. J. 379, 513-525.
85. Perkins, N. D. (2006). Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway. Oncogene 25, 6717-6730.
86. Pickart, C. M. (1997). Targeting of substrates to the 26S proteasome. FASEB J. 11, 1055-1066.
87. Prakash, S., Inobe, T., Hatch, A. J. and Matouschek, A. (2009). Substrate selection by the proteasome during degradation of protein complexes. Nat. Chem. Biol. 5, 29-36.
88. Rahighi, S., Ikeda, F., Kawasaki, M., Akutsu, M., Suzuki, N., Kato, R., Kensche, T., Uejima, T., Bloor, S., Komander, D. et al. (2009). Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell 136, 1098-1109.
89. Razani, B., Zarnegar, B., Ytterberg, A. J., Shiba, T., Dempsey, P. W., Ware, C. F., Loo, J. A. and Cheng, G. (2010). Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation. Sci. Signal. 3, ra41.
90. Rothwarf, D. M., Zandi, E., Natoli, G. and Karin, M. (1998). IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature 395, 297-300
91. Ruland, J. (2011). Return to homeostasis: downregulation of NF-kappaB responses. Nat. Immunol. 12, 709-714.
92. Schmidt, C., Peng, B., Li, Z., Sclabas, G. M., Fujioka, S., Niu, J., Schmidt-Supprian, M., Evans, D. B., Abbruzzese, J. L. and Chiao, P. J. (2003). Mechanisms of proinflammatory cytokine-induced biphasic NF-kappaB activation. Mol. Cell 12, 1287-1300.
93. Schmitz, M. L., Bacher, S. and Kracht, M. (2001). I kappa B-independent control of NF-kappa B activity by modulatory phosphorylations. Trends Biochem. Sci. 26, 186-190.
94. Schweitzer, K., Bozko, P. M., Dubiel, W. and Naumann, M. (2007). CSN controls NFkappaB by deubiquitinylation of IkappaBalpha. EMBO J. 26, 1532-1541.
95. Sebban, H., Yamaoka, S. and Courtois, G. (2006). Posttranslational modifications of NEMO and its partners in NF-kappaB signaling. Trends Cell. Biol. 16, 569-577.
96. 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-Uev1A/TNF receptor-associated factor 2 (TRAF2). J. Biol. Chem. 278, 15429-15434.
97. 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 TGF-beta signal transduction. Science 272, 1179-1182.
98. Shifera, A. S. (2010). The zinc finger domain of IKKgamma (NEMO) protein in health and disease. J. Cell. Mol. Med. 14, 2404-2414.
99. Shih, V. F., Tsui, R., Caldwell, A. and Hoffmann, A. (2011). A single NFkappaB system for both canonical and non-canonical signaling. Cell Res. 21, 86-102.
100. Shirane, M., Hatakeyama, S., Hattori, K. and Nakayama, K. (1999). Common pathway for the ubiquitination of IkappaBalpha, IkappaBbeta, and IkappaBepsilon mediated by the F-box protein FWD1. J. Biol. Chem. 274, 28169-28174.
101. Sun, S. C. (2011). Non-canonical NF-kappaB signaling pathway. Cell Res. 21, 71-85.
102. Sun, W., Tan, X., Shi, Y., Xu, G., Mao, R., Gu, X., Fan, Y., Yu, Y., Burlingame, S., Zhang, H. et al. (2010). USP11 negatively regulates TNFalpha-induced NF-kappaB activation by targeting on IkappaBalpha. Cell Signal. 22, 386-394.
103. Tang, E. D., Wang, C. Y., Xiong, Y. and Guan, K. L. (2003). A role for NF-kappaB essential modifier/IkappaB kinase-gamma (NEMO/IKKgamma) ubiquitination in the activation of the IkappaB kinase complex by tumor necrosis factor-alpha. J. Biol. Chem. 278, 37297-37305.
104. Thrower, J. S., Hoffman, L., Rechsteiner, M. and Pickart, C. M. (2000). Recognition of the polyubiquitin proteolytic signal. EMBO J. 19, 94-102.
105. Tokunaga, F., Sakata, S., Saeki, Y., Satomi, Y., Kirisako, T., Kamei, K., Nakagawa, T., Kato, M., Murata, S., Yamaoka, S. et al. (2009). Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat. Cell Biol. 11, 123-132.
106. Tokunaga, F., Nakagawa, T., Nakahara, M., Saeki, Y., Taniguchi, M., Sakata, S., Tanaka, K., Nakano, H. and Iwai, K. (2011). SHARPIN is a component of the NFkappaB-activating linear ubiquitin chain assembly complex. Nature 471, 633-636.
107. Trompouki, E., Hatzivassiliou, E., Tsichritzis, T., Farmer, H., Ashworth, A. and Mosialos, G. (2003). CYLD is a deubiquitinating enzyme that negatively regulates NFkappaB activation by TNFR family members. Nature 424, 793-796.
108. Vallabhapurapu, S., Matsuzawa, A., Zhang, W., Tseng, P. H., Keats, J. J., Wang, H., Vignali, D. A., Bergsagel, P. L. and Karin, M. (2008). Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nat. Immunol. 9, 1364-1370.
109. van Nocker, S. and Vierstra, R. D. (1993). Multiubiquitin chains linked through lysine 48 are abundant in vivo and are competent intermediates in the ubiquitin proteolytic pathway. J. Biol. Chem. 268, 24766-24773.
110. Verhelst, K., Verstrepen, L., Carpentier, I. and Beyaert, R. (2011). Linear ubiquitination in NF-kappaB signaling and inflammation: what we do understand and what we do not. Biochem. Pharmacol. 82, 1057-1065.
111. Viatour, P., Merville, M. P., Bours, V. and Chariot, A. (2005). Phosphorylation of NFkappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem. Sci. 30, 43-52.
112. Vince, J. E., Chau, D., Callus, B., Wong, W. W., Hawkins, C. J., Schneider, P., McKinlay, M., Benetatos, C. A., Condon, S. M., Chunduru, S. K. et al. (2008). TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFalpha. J. Cell Biol. 182, 171-184.
113. Vince, J. E., Pantaki, D., Feltham, R., Mace, P. D., Cordier, S. M., Schmukle, A. C., Davidson, A. J., Callus, B. A., Wong, W. W., Gentle, I. E. et al. (2009). TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis. J. Biol. Chem. 284, 35906-35915.
114. Wagner, S., Carpentier, I., Rogov, V., Kreike, M., Ikeda, F., Lohr, F., Wu, C. J., Ashwell, J. D., Dotsch, V., Dikic, I. et al. (2008). Ubiquitin binding mediates the NFkappaB inhibitory potential of ABIN proteins. Oncogene 27, 3739-3745.
115. Wajant, H. and Scheurich, P. (2011). TNFR1-induced activation of the classical NFkappaB pathway. FEBS J. 278, 862-876.
116. Walczak, H. (2011). TNF and ubiquitin at the crossroads of gene activation, cell death, inflammation, and cancer. Immunol. Rev. 244, 9-28.
117. 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.
118. Wertz, I. E. and Dixit, V. M. (2010). Signaling to NF-kappaB: regulation by ubiquitination. Cold Spring Harb. Perspect. Biol. 2, a003350.
119. 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-kappaB signalling. Nature 430, 694-699.
120. Windheim, M., Stafford, M., Peggie, M. and Cohen, P. (2008). Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase. Mol. Cell. Biol. 28, 1783-1791.
121. Wu, C. and Ghosh, S. (1999). beta-TrCP mediates the signal-induced ubiquitination of IkappaBbeta. J. Biol. Chem. 274, 29591-29594.
122. Wu, C. J. and Ashwell, J. D. (2008). NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation. Proc. Natl. Acad. Sci. USA 105, 3023-3028.
123. 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 [corrected]. Nat. Cell. Biol. 8, 398-406.
124. Wu, Z. H., Wong, E. T., Shi, Y., Niu, J., Chen, Z., Miyamoto, S. and Tergaonkar, V. (2010). ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress. Mol. Cell 40, 75-86.
125. Wullaert, A., Bonnet, M. C. and Pasparakis, M. (2011). NF-kappaB in the regulation of epithelial homeostasis and inflammation. Cell Res. 21, 146-158.
126. Xiao, G., Harhaj, E. W. and Sun, S. C. (2001). NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol. Cell 7, 401-409.
127. Xiao, G., Fong, A. and Sun, S. C. (2004). Induction of p100 processing by NF-kappaBinducing kinase involves docking IkappaB kinase alpha (IKKalpha) to p100 and IKKalpha-mediated phosphorylation. J. Biol. Chem. 279, 30099-30105.
128. Xu, G., Tan, X., Wang, H., Sun, W., Shi, Y., Burlingame, S., Gu, X., Cao, G., Zhang, T., Qin, J. et al. (2010). Ubiquitin-specific peptidase 21 inhibits tumor necrosis factor alpha-induced nuclear factor kappaB activation via binding to and deubiquitinating receptor-interacting protein 1. J. Biol. Chem. 285, 969-978.
129. Xu, M., Skaug, B., Zeng, W. and Chen, Z. J. (2009). A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFalpha and IL-1beta. Mol. Cell 36, 302-314.
130. 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.
131. 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-kappaB activation. Nat. Immunol. 2, 620-624.
132. Yang, Y., Yin, C., Pandey, A., Abbott, D., Sassetti, C. and Kelliher, M. A. (2007). NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J. Biol. Chem. 282, 36223-36229.
133. Yang, Y., Xia, F., Hermance, N., Mabb, A., Simonson, S., Morrissey, S., Gandhi, P., Munson, M., Miyamoto, S. and Kelliher, M. A. (2011). A cytosolic ATM/NEMO/RIP1 complex recruits TAK1 to mediate the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage. Mol. Cell. Biol. 31, 2774-2786.
134. Yaron, A., Hatzubai, A., Davis, M., Lavon, I., Amit, S., Manning, A. M., Andersen, J. S., Mann, M., Mercurio, F. and Ben-Neriah, Y. (1998). Identification of the receptor component of the IkappaBalpha-ubiquitin ligase. Nature 396, 590-594.
135. Yoshikawa, A., Sato, Y., Yamashita, M., Mimura, H., Yamagata, A. and Fukai, S. (2009). Crystal structure of the NEMO ubiquitin-binding domain in complex with Lys 63-linked di-ubiquitin. FEBS Lett. 583, 3317-3322.
136. Zarnegar, B., Yamazaki, S., He, J. Q. and Cheng, G. (2008). Control of canonical NFkappaB activation through the NIK-IKK complex pathway. Proc. Natl. Acad. Sci. USA 105, 3503-3508.
137. Zheng, C., Yin, Q. and Wu, H. (2011). Structural studies of NF-kappaB signaling. Cell Res. 21, 183-195.
138. Zhu, G., Wu, C. J., Zhao, Y. and Ashwell, J. D. (2007). Optineurin negatively regulates TNFalpha- induced NF-kappaB activation by competing with NEMO for ubiquitinated RIP. Curr. Biol. 17, 1438-1443.