30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology

Cell

Volumn 168, Issue 1-2, 2017, Pages 37-57

  Zhang, Qian ^a   Lenardo, Michael J ^b   Baltimore, David ^c  

^a SIDRA MEDICAL AND RESEARCH CENTER   (Qatar)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^c California Institute of Technology   (United States)

Author keywords

gene regulation; genetic disease; genomics; human gene; I B; immunity; lymphocyte; NF B; Rel; transactivator

Indexed keywords

A20 PROTEIN; CARD11 PROTEIN; CARD14 PROTEIN; CARD9 PROTEIN; CASPASE 8; CYLINDROMATOSIS PROTEIN; ECTODYSPLASIN A; HOIL1 PROTEIN; HOIP PROTEIN; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MALT LYMPHOMA TRANSLOCATION PROTEIN 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE 7; NFKB1 PROTEIN; NFKB2 PROTEIN; NIK PROTEIN; OTULIN PROTEIN; PROTEIN; PROTEIN BCL 10; PROTEIN P100; PROTEIN P52; TRANSCRIPTION FACTOR REL; TRANSFORMING GROWTH FACTOR BETA ACTIVATED KINASE 1; TRAPPC9 PROTEIN; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UNCLASSIFIED DRUG;

BIOCHEMISTRY; DEVELOPMENTAL DISORDER; GENE MUTATION; HUMAN; HUMAN GENETICS; IMMUNE DEFICIENCY; IMMUNE DYSREGULATION; MALIGNANT NEOPLASM; MONOGENIC DISORDER; NONHUMAN; PATHOLOGY; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN TARGETING; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; SOMATIC MUTATION; UBIQUITINATION; ANIMAL; CHEMISTRY; GENETICS; HISTORY; IMMUNOLOGY; INFLAMMATION; METABOLISM; MOUSE; MUTATION;

ANIMALS; HISTORY, 20TH CENTURY; HISTORY, 21ST CENTURY; HUMANS; INFLAMMATION; MICE; MUTATION; NF-KAPPA B; SIGNAL TRANSDUCTION;

EID: 85009187552     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2016.12.012     Document Type: Review

References (140)

1. Andersen, L.L., Mørk, N., Reinert, L.S., Kofod-Olsen, E., Narita, R., Jørgensen, S.E., Skipper, K.A., Höning, K., Gad, H.H., Østergaard, L., et al. Functional IRF3 deficiency in a patient with herpes simplex encephalitis. J. Exp. Med. 212 (2015), 1371–1379.
2. Audry, M., Ciancanelli, M., Yang, K., Cobat, A., Chang, H.H., Sancho-Shimizu, V., Lorenzo, L., Niehues, T., Reichenbach, J., Li, X.X., et al. NEMO is a key component of NF-kappaB- and IRF-3-dependent TLR3-mediated immunity to herpes simplex virus. J. Allergy Clin. Immunol. 128 (2011), 610–617.
3. Baltimore, D., NF-κB is 25. Nat. Immunol. 12 (2011), 683–685.
4. Basak, S., Kim, H., Kearns, J.D., Tergaonkar, V., O'Dea, E., Werner, S.L., Benedict, C.A., Ware, C.F., Ghosh, G., Verma, I.M., Hoffmann, A., A fourth IkappaB protein within the NF-kappaB signaling module. Cell 128 (2007), 369–381.
5. Basart, H., van de Kar, A., Adès, L., Cho, T.J., Carter, E., Maas, S.M., Wilson, L.C., van der Horst, C.M., Wade, E.M., Robertson, S.P., Hennekam, R.C., Frontometaphyseal dysplasia and keloid formation without FLNA mutations. Am. J. Med. Genet. A. 167 (2015), 1215–1222.
6. Ben-Neriah, Y., Regulatory functions of ubiquitination in the immune system. Nat. Immunol. 3 (2002), 20–26.
7. Bidère, N., Ngo, V.N., Lee, J., Collins, C., Zheng, L., Wan, F., Davis, R.E., Lenz, G., Anderson, D.E., Arnoult, D., et al. Casein kinase 1alpha governs antigen-receptor-induced NF-kappaB activation and human lymphoma cell survival. Nature 458 (2009), 92–96.
8. Biggs, P.J., Wooster, R., Ford, D., Chapman, P., Mangion, J., Quirk, Y., Easton, D.F., Burn, J., Stratton, M.R., Familial cylindromatosis (turban tumour syndrome) gene localised to chromosome 16q12-q13: Evidence for its role as a tumour suppressor gene. Nat. Genet. 11 (1995), 441–443.
9. Bignell, G.R., Warren, W., Seal, S., Takahashi, M., Rapley, E., Barfoot, R., Green, H., Brown, C., Biggs, P.J., Lakhani, S.R., et al. Identification of the familial cylindromatosis tumour-suppressor gene. Nat. Genet. 25 (2000), 160–165.
10. Blonska, M., Lin, X., NF-κB signaling pathways regulated by CARMA family of scaffold proteins. Cell Res. 21 (2011), 55–70.
11. Boisson, B., Laplantine, E., Prando, C., Giliani, S., Israelsson, E., Xu, Z., Abhyankar, A., Israël, L., Trevejo-Nunez, G., Bogunovic, D., et al. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat. Immunol. 13 (2012), 1178–1186.
12. Boisson, B., Laplantine, E., Dobbs, K., Cobat, A., Tarantino, N., Hazen, M., Lidov, H.G., Hopkins, G., Du, L., Belkadi, A., et al. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia. J. Exp. Med. 212 (2015), 939–951.
13. Boztug, H., Hirschmugl, T., Holter, W., Lakatos, K., Kager, L., Trapin, D., Pickl, W., Förster-Waldl, E., Boztug, K., NF-κB1 haploinsufficiency causing immunodeficiency and EBV-driven lymphoproliferation. J. Clin. Immunol. 36 (2016), 533–540.
14. Brightbill, H.D., Jackman, J.K., Suto, E., Kennedy, H., Jones, C. 3rd, Chalasani, S., Lin, Z., Tam, L., Roose-Girma, M., Balazs, M., et al. Conditional deletion of NF-κB-inducing kinase (NIK) in adult mice disrupts mature B cell survival and activation. J. Immunol. 195 (2015), 953–964.
15. Buchbinder, D., Stinson, J.R., Nugent, D.J., Heurtier, L., Suarez, F., Sukumar, G., Dalgard, C.L., Masson, C., Parisot, M., Zhang, Y., et al. Mild B-cell lymphocytosis in patients with a CARD11 C49Y mutation. J. Allergy Clin. Immunol. 136 (2015), 819–821.
16. Charbit-Henrion, F., Jeverica, A.K., Begue, B., Markelj, G., Parlato, M., Avcin, S.L., Callebaut, I., Bras, M., Parisot, M., Jazbec, J., et al. Deficiency in mucosa associated lymphoid tissue lymphoma translocation 1 (MALT1): A novel cause of Ipex-like syndrome. J. Pediatr. Gastroenterol. Nutr., 2016 Published online: June 2, 2016.
17. Chen, K., Coonrod, E.M., Kumánovics, A., Franks, Z.F., Durtschi, J.D., Margraf, R.L., Wu, W., Heikal, N.M., Augustine, N.H., Ridge, P.G., et al. Germline mutations in NFKB2 implicate the noncanonical NF-κB pathway in the pathogenesis of common variable immunodeficiency. Am. J. Hum. Genet. 93 (2013), 812–824.
18. Chun, H.J., Zheng, L., Ahmad, M., Wang, J., Speirs, C.K., Siegel, R.M., Dale, J.K., Puck, J., Davis, J., Hall, C.G., et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 419 (2002), 395–399.
19. Corda, G., Sala, A., Cutaneous cylindroma: It's all about MYB. J. Pathol. 239 (2016), 391–393.
20. Courtois, G., Smahi, A., Reichenbach, J., Döffinger, R., Cancrini, C., Bonnet, M., Puel, A., Chable-Bessia, C., Yamaoka, S., Feinberg, J., et al. A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J. Clin. Invest. 112 (2003), 1108–1115.
21. Courtois, G., Pescatore, A., Gautheron, J., Fusco, F., Ursini, M.V., Senegas, A., NF-KB-Related Genetic Diseases. 2016, Springer Berlin Heidelberg.
22. Couzin-Frankel, J., Breakthrough of the year 2013. Cancer immunotherapy. Science 342 (2013), 1432–1433.
23. Damgaard, R.B., Walker, J.A., Marco-Casanova, P., Morgan, N.V., Titheradge, H.L., Elliott, P.R., McHale, D., Maher, E.R., McKenzie, A.N., Komander, D., The deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity. Cell 166 (2016), 1215–1230.
24. Dierlamm, J., Baens, M., Wlodarska, I., Stefanova-Ouzounova, M., Hernandez, J.M., Hossfeld, D.K., De Wolf-Peeters, C., Hagemeijer, A., Van den Berghe, H., Marynen, P., The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. Blood 93 (1999), 3601–3609.
25. Döffinger, R., Smahi, A., Bessia, C., Geissmann, F., Feinberg, J., Durandy, A., Bodemer, C., Kenwrick, S., Dupuis-Girod, S., Blanche, S., et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat. Genet. 27 (2001), 277–285.
26. Dondelinger, Y., Darding, M., Bertrand, M.J., Walczak, H., Poly-ubiquitination in TNFR1-mediated necroptosis. Cell. Mol. Life Sci. 73 (2016), 2165–2176.
27. Duong, B.H., Onizawa, M., Oses-Prieto, J.A., Advincula, R., Burlingame, A., Malynn, B.A., Ma, A., A20 restricts ubiquitination of pro-interleukin-1β protein complexes and suppresses NLRP3 inflammasome activity. Immunity 42 (2015), 55–67.
28. Egawa, T., Albrecht, B., Favier, B., Sunshine, M.J., Mirchandani, K., O'Brien, W., Thome, M., Littman, D.R., Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation. Curr. Biol. 13 (2003), 1252–1258.
29. Elgueta, R., Benson, M.J., de Vries, V.C., Wasiuk, A., Guo, Y., Noelle, R.J., Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol. Rev. 229 (2009), 152–172.
30. Farkas, K., Deák, B.K., Sánchez, L.C., Martínez, A.M., Corell, J.J., Botella, A.M., Benito, G.M., López, R.R., Vanecek, T., Kazakov, D.V., et al. The CYLD p.R758X worldwide recurrent nonsense mutation detected in patients with multiple familial trichoepithelioma type 1, Brooke-Spiegler syndrome and familial cylindromatosis represents a mutational hotspot in the gene. BMC Genet., 17, 2016, 36.
31. Filipe-Santos, O., Bustamante, J., Haverkamp, M.H., Vinolo, E., Ku, C.L., Puel, A., Frucht, D.M., Christel, K., von Bernuth, H., Jouanguy, E., et al. X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production. J. Exp. Med. 203 (2006), 1745–1759.
32. Fliegauf, M., Bryant, V.L., Frede, N., Slade, C., Woon, S.T., Lehnert, K., Winzer, S., Bulashevska, A., Scerri, T., Leung, E., et al. Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency. Am. J. Hum. Genet. 97 (2015), 389–403.
33. Fuchs, S., Rensing-Ehl, A., Pannicke, U., Lorenz, M.R., Fisch, P., Jeelall, Y., Rohr, J., Speckmann, C., Vraetz, T., Farmand, S., et al. Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency. Blood 126 (2015), 1658–1669.
34. Fuchs-Telem, D., Sarig, O., van Steensel, M.A., Isakov, O., Israeli, S., Nousbeck, J., Richard, K., Winnepenninckx, V., Vernooij, M., Shomron, N., et al. Familial pityriasis rubra pilaris is caused by mutations in CARD14. Am. J. Hum. Genet. 91 (2012), 163–170.
35. Gavino, C., Hamel, N., Zeng, J.B., Legault, C., Guiot, M.C., Chankowsky, J., Lejtenyi, D., Lemire, M., Alarie, I., Dufresne, S., et al. Impaired RASGRF1/ERK-mediated GM-CSF response characterizes CARD9 deficiency in French-Canadians. J. Allergy Clin. Immunol. 137 (2016), 1178–1188.
36. Gerondakis, S., Siebenlist, U., Roles of the NF-kappaB pathway in lymphocyte development and function. Cold Spring Harb. Perspect. Biol., 2, 2010, a000182.
37. Gerondakis, S., Grumont, R., Gugasyan, R., Wong, L., Isomura, I., Ho, W., Banerjee, A., Unravelling the complexities of the NF-kappaB signalling pathway using mouse knockout and transgenic models. Oncogene 25 (2006), 6781–6799.
38. Glocker, E.O., Hennigs, A., Nabavi, M., Schäffer, A.A., Woellner, C., Salzer, U., Pfeifer, D., Veelken, H., Warnatz, K., Tahami, F., et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med. 361 (2009), 1727–1735.
39. Greil, J., Rausch, T., Giese, T., Bandapalli, O.R., Daniel, V., Bekeredjian-Ding, I., Stutz, A.M., Drees, C., Roth, S., Ruland, J., et al. Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency. J. Allergy Clin. Immunol. 131 (2013), 1376–1383.
40. Guo, Y., Audry, M., Ciancanelli, M., Alsina, L., Azevedo, J., Herman, M., Anguiano, E., Sancho-Shimizu, V., Lorenzo, L., Pauwels, E., et al. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J. Exp. Med. 208 (2011), 2083–2098.
41. Hachmann, J., Salvesen, G.S., The Paracaspase MALT1. Biochimie 122 (2016), 324–338.
42. Hara, H., Wada, T., Bakal, C., Kozieradzki, I., Suzuki, S., Suzuki, N., Nghiem, M., Griffiths, E.K., Krawczyk, C., Bauer, B., et al. The MAGUK family protein CARD11 is essential for lymphocyte activation. Immunity 18 (2003), 763–775.
43. Harden, J.L., Krueger, J.G., Bowcock, A.M., The immunogenetics of psoriasis: A comprehensive review. J. Autoimmun. 64 (2015), 66–73.
44. Hayden, M.S., Ghosh, S., Shared principles in NF-kappaB signaling. Cell 132 (2008), 344–362.
45. Hayden, M.S., Ghosh, S., NF-κB, the first quarter-century: Remarkable progress and outstanding questions. Genes Dev. 26 (2012), 203–234.
46. Headon, D.J., Emmal, S.A., Ferguson, B.M., Tucker, A.S., Justice, M.J., Sharpe, P.T., Zonana, J., Overbeek, P.A., Gene defect in ectodermal dysplasia implicates a death domain adapter in development. Nature 414 (2001), 913–916.
47. Herman, M., Ciancanelli, M., Ou, Y.H., Lorenzo, L., Klaudel-Dreszler, M., Pauwels, E., Sancho-Shimizu, V., Pérez de Diego, R., Abhyankar, A., Israelsson, E., et al. Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood. J. Exp. Med. 209 (2012), 1567–1582.
48. Hu, W.H., Pendergast, J.S., Mo, X.M., Brambilla, R., Bracchi-Ricard, V., Li, F., Walters, W.M., Blits, B., He, L., Schaal, S.M., Bethea, J.R., NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation. J. Biol. Chem. 280 (2005), 29233–29241.
49. Hubeau, M., Ngadjeua, F., Puel, A., Israel, L., Feinberg, J., Chrabieh, M., Belani, K., Bodemer, C., Fabre, I., Plebani, A., et al. New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: Impairment of ubiquitin binding despite normal folding of NEMO protein. Blood 118 (2011), 926–935.
50. Iwai, K., Diverse roles of the ubiquitin system in NF-κB activation. Biochim. Biophys. Acta 1843 (2014), 129–136.
51. Jabara, H.H., Ohsumi, T., Chou, J., Massaad, M.J., Benson, H., Megarbane, A., Chouery, E., Mikhael, R., Gorka, O., Gewies, A., et al. A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency. J. Allergy Clin. Immunol. 132 (2013), 151–158.
52. Jordan, C.T., Cao, L., Roberson, E.D., Duan, S., Helms, C.A., Nair, R.P., Duffin, K.C., Stuart, P.E., Goldgar, D., Hayashi, G., et al. Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. Am. J. Hum. Genet. 90 (2012), 796–808.
53. Juilland, M., Thome, M., Role of the CARMA1/BCL10/MALT1 complex in lymphoid malignancies. Curr. Opin. Hematol. 23 (2016), 402–409.
54. Kalay, E., Sezgin, O., Chellappa, V., Mutlu, M., Morsy, H., Kayserili, H., Kreiger, E., Cansu, A., Toraman, B., Abdalla, E.M., et al. Mutations in RIPK4 cause the autosomal-recessive form of popliteal pterygium syndrome. Am. J. Hum. Genet. 90 (2012), 76–85.
55. Karin, M., Lin, A., NF-kappaB at the crossroads of life and death. Nat. Immunol. 3 (2002), 221–227.
56. Katakam, A.K., Brightbill, H., Franci, C., Kung, C., Nunez, V., Jones, C. 3rd, Peng, I., Jeet, S., Wu, L.C., Mellman, I., et al. Dendritic cells require NIK for CD40-dependent cross-priming of CD8+ T cells. Proc. Natl. Acad. Sci. USA 112 (2015), 14664–14669.
57. Kere, J., Srivastava, A.K., Montonen, O., Zonana, J., Thomas, N., Ferguson, B., Munoz, F., Morgan, D., Clarke, A., Baybayan, P., et al. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat. Genet. 13 (1996), 409–416.
58. Keusekotten, K., Elliott, P.R., Glockner, L., Fiil, B.K., Damgaard, R.B., Kulathu, Y., Wauer, T., Hospenthal, M.K., Gyrd-Hansen, M., Krappmann, D., et al. OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell 153 (2013), 1312–1326.
59. Kim, H.J., Hawke, N., Baldwin, A.S., NF-kappaB and IKK as therapeutic targets in cancer. Cell Death Differ. 13 (2006), 738–747.
60. Kovalenko, A., Chable-Bessia, C., Cantarella, G., Israël, A., Wallach, D., Courtois, G., The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature 424 (2003), 801–805.
61. Lafaille, F.G., Pessach, I.M., Zhang, S.Y., Ciancanelli, M.J., Herman, M., Abhyankar, A., Ying, S.W., Keros, S., Goldstein, P.A., Mostoslavsky, G., et al. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature 491 (2012), 769–773.
62. Lahtela, J., Nousiainen, H.O., Stefanovic, V., Tallila, J., Viskari, H., Karikoski, R., Gentile, M., Saloranta, C., Varilo, T., Salonen, R., Kestilä, M., Mutant CHUK and severe fetal encasement malformation. N. Engl. J. Med. 363 (2010), 1631–1637.
63. Lanternier, F., Pathan, S., Vincent, Q.B., Liu, L., Cypowyj, S., Prando, C., Migaud, M., Taibi, L., Ammar-Khodja, A., Boudghene Stambouli, O., et al. Deep dermatophytosis and inherited CARD9 deficiency. N. Engl. J. Med. 369 (2013), 1704–1714.
64. Lanternier, F., Mahdaviani, S.A., Barbati, E., Chaussade, H., Koumar, Y., Levy, R., Denis, B., Brunel, A.S., Martin, S., Loop, M., et al. Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, or both. J. Allergy Clin. Immunol. 135 (2015), 1558–1568.
65. Lee, C.E., Fulcher, D.A., Whittle, B., Chand, R., Fewings, N., Field, M., Andrews, D., Goodnow, C.C., Cook, M.C., Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood 124 (2014), 2964–2972.
66. Lemmers, B., Salmena, L., Bidère, N., Su, H., Matysiak-Zablocki, E., Murakami, K., Ohashi, P.S., Jurisicova, A., Lenardo, M., Hakem, R., Hakem, A., Essential role for caspase-8 in Toll-like receptors and NFkappaB signaling. J. Biol. Chem. 282 (2007), 7416–7423.
67. Lenardo, M., Pierce, J.W., Baltimore, D., Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science 236 (1987), 1573–1577.
68. Lenardo, M.J., Fan, C.M., Maniatis, T., Baltimore, D., The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction. Cell 57 (1989), 287–294.
69. Lenz, G., Davis, R.E., Ngo, V.N., Lam, L., George, T.C., Wright, G.W., Dave, S.S., Zhao, H., Xu, W., Rosenwald, A., et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319 (2008), 1676–1679.
70. Liu, F., Xia, Y., Parker, A.S., Verma, I.M., IKK biology. Immunol. Rev. 246 (2012), 239–253.
71. Lopez-Granados, E., Keenan, J.E., Kinney, M.C., Leo, H., Jain, N., Ma, C.A., Quinones, R., Gelfand, E.W., Jain, A., A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency. Hum. Mutat. 29 (2008), 861–868.
72. Lougaris, V., Tabellini, G., Vitali, M., Baronio, M., Patrizi, O., Tampella, G., Biasini, A., Moratto, D., Parolini, S., Plebani, A., Defective natural killer-cell cytotoxic activity in NFKB2-mutated CVID-like disease. J. Allergy Clin. Immunol. 135 (2015), 1641–1643.
73. Ma, A., Malynn, B.A., A20: Linking a complex regulator of ubiquitylation to immunity and human disease. Nat. Rev. Immunol. 12 (2012), 774–785.
74. Ma, X., Becker Buscaglia, L.E., Barker, J.R., Li, Y., MicroRNAs in NF-kappaB signaling. J. Mol. Cell Biol. 3 (2011), 159–166.
75. MacDuff, D.A., Reese, T.A., Kimmey, J.M., Weiss, L.A., Song, C., Zhang, X., Kambal, A., Duan, E., Carrero, J.A., Boisson, B., et al. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection. eLife, 4, 2015, 4.
76. Mackay, F., Cancro, M.P., Travelling with the BAFF/BLyS family: Are we there yet?. Semin. Immunol. 18 (2006), 261–262.
77. Massoumi, R., Chmielarska, K., Hennecke, K., Pfeifer, A., Fässler, R., Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling. Cell 125 (2006), 665–677.
78. Mathis, B.J., Lai, Y., Qu, C., Janicki, J.S., Cui, T., CYLD-mediated signaling and diseases. Curr. Drug Targets 16 (2015), 284–294.
79. McDonald, D.R., Mooster, J.L., Reddy, M., Bawle, E., Secord, E., Geha, R.S., Heterozygous N-terminal deletion of IkappaBalpha results in functional nuclear factor kappaB haploinsufficiency, ectodermal dysplasia, and immune deficiency. J. Allergy Clin. Immunol. 120 (2007), 900–907.
80. Meylan, E., Tschopp, J., The RIP kinases: Crucial integrators of cellular stress. Trends Biochem. Sci. 30 (2005), 151–159.
81. Mina, R., Cerrato, C., Bernardini, A., Aghemo, E., Palumbo, A., New pharmacotherapy options for multiple myeloma. Expert Opin. Pharmacother. 17 (2016), 181–192.
82. Mir, A., Kaufman, L., Noor, A., Motazacker, M.M., Jamil, T., Azam, M., Kahrizi, K., Rafiq, M.A., Weksberg, R., Nasr, T., et al. Identification of mutations in TRAPPC9, which encodes the NIK- and IKK-beta-binding protein, in nonsyndromic autosomal-recessive mental retardation. Am. J. Hum. Genet. 85 (2009), 909–915.
83. Mochida, G.H., Mahajnah, M., Hill, A.D., Basel-Vanagaite, L., Gleason, D., Hill, R.S., Bodell, A., Crosier, M., Straussberg, R., Walsh, C.A., A truncating mutation of TRAPPC9 is associated with autosomal-recessive intellectual disability and postnatal microcephaly. Am. J. Hum. Genet. 85 (2009), 897–902.
84. Mooster, J.L., Le Bras, S., Massaad, M.J., Jabara, H., Yoon, J., Galand, C., Heesters, B.A., Burton, O.T., Mattoo, H., Manis, J., Geha, R.S., Defective lymphoid organogenesis underlies the immune deficiency caused by a heterozygous S32I mutation in IκBα. J. Exp. Med. 212 (2015), 185–202.
85. Mousallem, T., Yang, J., Urban, T.J., Wang, H., Adeli, M., Parrott, R.E., Roberts, J.L., Goldstein, D.B., Buckley, R.H., Zhong, X.P., A nonsense mutation in IKBKB causes combined immunodeficiency. Blood 124 (2014), 2046–2050.
86. Neoptolemos, J.P., Stocken, D.D., Bassi, C., Ghaneh, P., Cunningham, D., Goldstein, D., Padbury, R., Moore, M.J., Gallinger, S., Mariette, C., et al., European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: A randomized controlled trial. JAMA 304 (2010), 1073–1081.
87. Ngo, V.N., Davis, R.E., Lamy, L., Yu, X., Zhao, H., Lenz, G., Lam, L.T., Dave, S., Yang, L., Powell, J., Staudt, L.M., A loss-of-function RNA interference screen for molecular targets in cancer. Nature 441 (2006), 106–110.
88. Niemela, J., Kuehn, H.S., Kelly, C., Zhang, M., Davies, J., Melendez, J., Dreiling, J., Kleiner, D., Calvo, K., Oliveira, J.B., Rosenzweig, S.D., Caspase-8 deficiency presenting as late-onset multi-organ lymphocytic infiltration with granulomas in two adult siblings. J. Clin. Immunol. 35 (2015), 348–355.
89. Nishikori, M., Classical and alternative NF-kB activation pathways and their roles in lymphoid malignancies. J. Clin. Exp. Hematop., 45, 2005, 9.
90. Noma, H., Eshima, K., Satoh, M., Iwabuchi, K., Differential dependence on nuclear factor-κB-inducing kinase among natural killer T-cell subsets in their development. Immunology 146 (2015), 89–99.
91. Ohnishi, H., Kawamoto, N., Seishima, M., Ohara, O., Fukao, T., A Japanese family case with juvenile onset Behçet's disease caused by TNFAIP3 mutation. Allergol. Int., 2016, 10.1016/j.alit.2016.06.006 Published online: July 19, 2016.
92. Olivier, S., Close, P., Castermans, E., de Leval, L., Tabruyn, S., Chariot, A., Malaise, M., Merville, M.P., Bours, V., Franchimont, N., Raloxifene-induced myeloma cell apoptosis: A study of nuclear factor-kappaB inhibition and gene expression signature. Mol. Pharmacol. 69 (2006), 1615–1623.
93. Pannicke, U., Baumann, B., Fuchs, S., Henneke, P., Rensing-Ehl, A., Rizzi, M., Janda, A., Hese, K., Schlesier, M., Holzmann, K., et al. Deficiency of innate and acquired immunity caused by an IKBKB mutation. N. Engl. J. Med. 369 (2013), 2504–2514.
94. Pasparakis, M., Courtois, G., Hafner, M., Schmidt-Supprian, M., Nenci, A., Toksoy, A., Krampert, M., Goebeler, M., Gillitzer, R., Israel, A., et al. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature 417 (2002), 861–866.
95. Pasqualucci, L., Dalla-Favera, R., The genetic landscape of diffuse large B-cell lymphoma. Semin. Hematol. 52 (2015), 67–76.
96. Peltzer, N., Rieser, E., Taraborrelli, L., Draber, P., Darding, M., Pernaute, B., Shimizu, Y., Sarr, A., Draberova, H., Montinaro, A., et al. HOIP deficiency causes embryonic lethality by aberrant TNFR1-mediated endothelial cell death. Cell Rep. 9 (2014), 153–165.
97. Pérez de Diego, R., Sancho-Shimizu, V., Lorenzo, L., Puel, A., Plancoulaine, S., Picard, C., Herman, M., Cardon, A., Durandy, A., Bustamante, J., et al. Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity 33 (2010), 400–411.
98. Perkins, N.D., The diverse and complex roles of NF-κB subunits in cancer. Nat. Rev. Cancer 12 (2012), 121–132.
99. Picard, C., Puel, A., Bonnet, M., Ku, C.L., Bustamante, J., Yang, K., Soudais, C., Dupuis, S., Feinberg, J., Fieschi, C., et al. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299 (2003), 2076–2079.
100. Price, S., Shaw, P.A., Seitz, A., Joshi, G., Davis, J., Niemela, J.E., Perkins, K., Hornung, R.L., Folio, L., Rosenberg, P.S., et al. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood 123 (2014), 1989–1999.
101. Rowe, A.M., Murray, S.E., Raué, H.P., Koguchi, Y., Slifka, M.K., Parker, D.C., A cell-intrinsic requirement for NF-κB-inducing kinase in CD4 and CD8 T cell memory. J. Immunol. 191 (2013), 3663–3672.
102. Ruefli-Brasse, A.A., French, D.M., Dixit, V.M., Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase. Science 302 (2003), 1581–1584.
103. Salmena, L., Lemmers, B., Hakem, A., Matysiak-Zablocki, E., Murakami, K., Au, P.Y., Berry, D.M., Tamblyn, L., Shehabeldin, A., Migon, E., et al. Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev. 17 (2003), 883–895.
104. Sancho-Shimizu, V., Pérez de Diego, R., Lorenzo, L., Halwani, R., Alangari, A., Israelsson, E., Fabrega, S., Cardon, A., Maluenda, J., Tatematsu, M., et al. Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J. Clin. Invest. 121 (2011), 4889–4902.
105. Sasaki, K., Iwai, K., Roles of linear ubiquitinylation, a crucial regulator of NF-κB and cell death, in the immune system. Immunol. Rev. 266 (2015), 175–189.
106. Schimke, L.F., Rieber, N., Rylaarsdam, S., Cabral-Marques, O., Hubbard, N., Puel, A., Kallmann, L., Sombke, S.A., Notheis, G., Schwarz, H.P., et al. A novel gain-of-function IKBA mutation underlies ectodermal dysplasia with immunodeficiency and polyendocrinopathy. J. Clin. Immunol. 33 (2013), 1088–1099.
107. Schmidt-Supprian, M., Bloch, W., Courtois, G., Addicks, K., Israël, A., Rajewsky, K., Pasparakis, M., NEMO/IKK gamma-deficient mice model incontinentia pigmenti. Mol. Cell 5 (2000), 981–992.
108. Sen, R., Baltimore, D., Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46 (1986), 705–716.
109. Sha, W.C., Liou, H.C., Tuomanen, E.I., Baltimore, D., Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell 80 (1995), 321–330.
110. Sharfe, N., Merico, D., Karanxha, A., Macdonald, C., Dadi, H., Ngan, B., Herbrick, J.A., Roifman, C.M., The effects of RelB deficiency on lymphocyte development and function. J. Autoimmun. 65 (2015), 90–100.
111. Shigemura, T., Kaneko, N., Kobayashi, N., Kobayashi, K., Takeuchi, Y., Nakano, N., Masumoto, J., Agematsu, K., Novel heterozygous C243Y A20/TNFAIP3 gene mutation is responsible for chronic inflammation in autosomal-dominant Behçet's disease. RMD Open, 2, 2016, e000223.
112. Smahi, A., Courtois, G., Vabres, P., Yamaoka, S., Heuertz, S., Munnich, A., Israël, A., Heiss, N.S., Klauck, S.M., Kioschis, P., et al., The International Incontinentia Pigmenti (IP) Consortium. Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. Nature 405 (2000), 466–472.
113. Smale, S.T., Dimer-specific regulatory mechanisms within the NF-κB family of transcription factors. Immunol. Rev. 246 (2012), 193–204.
114. Snow, A.L., Xiao, W., Stinson, J.R., Lu, W., Chaigne-Delalande, B., Zheng, L., Pittaluga, S., Matthews, H.F., Schmitz, R., Jhavar, S., et al. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. J. Exp. Med. 209 (2012), 2247–2261.
115. Stepensky, P., Keller, B., Buchta, M., Kienzler, A.K., Elpeleg, O., Somech, R., Cohen, S., Shachar, I., Miosge, L.A., Schlesier, M., et al. Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects. J. Allergy Clin. Immunol. 131 (2013), 477–485.
116. Su, H.C., Lenardo, M.J., Genetic defects of apoptosis and primary immunodeficiency. Immunol. Allergy Clin. North Am. 28 (2008), 329–351.
117. Su, H., Bidère, N., Zheng, L., Cubre, A., Sakai, K., Dale, J., Salmena, L., Hakem, R., Straus, S., Lenardo, M., Requirement for caspase-8 in NF-kappaB activation by antigen receptor. Science 307 (2005), 1465–1468.
118. Sugiura, K., The genetic background of generalized pustular psoriasis: IL36RN mutations and CARD14 gain-of-function variants. J. Dermatol. Sci. 74 (2014), 187–192.
119. Sun, S.C., Non-canonical NF-κB signaling pathway. Cell Res. 21 (2011), 71–85.
120. Sun, S.C., The noncanonical NF-κB pathway. Immunol. Rev. 246 (2012), 125–140.
121. Tanaka, M., Fuentes, M.E., Yamaguchi, K., Durnin, M.H., Dalrymple, S.A., Hardy, K.L., Goeddel, D.V., Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice. Immunity 10 (1999), 421–429.
122. Tokunaga, F., Linear ubiquitination-mediated NF-κB regulation and its related disorders. J. Biochem. 154 (2013), 313–323.
123. Torres, J.M., Martinez-Barricarte, R., García-Gómez, S., Mazariegos, M.S., Itan, Y., Boisson, B., Rholvarez, R., Jiménez-Reinoso, A., del Pino, L., Rodríguez-Pena, R., et al. Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity. J. Clin. Invest. 124 (2014), 5239–5248.
124. Trzeciak, W.H., Koczorowski, R., Molecular basis of hypohidrotic ectodermal dysplasia: An update. J. Appl. Genet. 57 (2016), 51–61.
125. Tsoi, L.C., Spain, S.L., Knight, J., Ellinghaus, E., Stuart, P.E., Capon, F., Ding, J., Li, Y., Tejasvi, T., Gudjonsson, J.E., et al. Collaborative Association Study of Psoriasis (CASP) Genetic Analysis of Psoriasis Consortium Psoriasis Association Genetics Extension, Wellcome Trust Case Control Consortium 2. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat. Genet. 44 (2012), 1341–1348.
126. Vande Walle, L., Van Opdenbosch, N., Jacques, P., Fossoul, A., Verheugen, E., Vogel, P., Beyaert, R., Elewaut, D., Kanneganti, T.D., van Loo, G., Lamkanfi, M., Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis. Nature 512 (2014), 69–73.
127. von Bernuth, H., Picard, C., Jin, Z., Pankla, R., Xiao, H., Ku, C.L., Chrabieh, M., Mustapha, I.B., Ghandil, P., Camcioglu, Y., et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321 (2008), 691–696.
128. Wade, E.M., Daniel, P.B., Jenkins, Z.A., McInerney-Leo, A., Leo, P., Morgan, T., Addor, M.C., Adès, L.C., Bertola, D., Bohring, A., et al. Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia. Am. J. Hum. Genet. 99 (2016), 392–406.
129. Weiss, K., Applegate, C., Wang, T., Batista, D.A., Familial TAB2 microdeletion and congenital heart defects including unusual valve dysplasia and tetralogy of fallot. Am. J. Med. Genet. A. 167A (2015), 2702–2706.
130. Wieacker, P., Zimmer, J., Ropers, H.H., X inactivation patterns in two syndromes with probable X-linked dominant, male lethal inheritance. Clin. Genet. 28 (1985), 238–242.
131. Willmann, K.L., Klaver, S., Doğu, F., Santos-Valente, E., Garncarz, W., Bilic, I., Mace, E., Salzer, E., Conde, C.D., Sic, H., et al. Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity. Nat. Commun., 5, 2014, 5360.
132. Wisniewski, S.A., Trzeciak, W.H., A new mutation resulting in the truncation of the TRAF6-interacting domain of XEDAR: A possible novel cause of hypohidrotic ectodermal dysplasia. J. Med. Genet. 49 (2012), 499–501.
133. Wisniewski, S.A., Trzeciak, W.H., A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia. Br. J. Dermatol. 166 (2012), 1353–1356.
134. Xue, L., Morris, S.W., Orihuela, C., Tuomanen, E., Cui, X., Wen, R., Wang, D., Defective development and function of Bcl10-deficient follicular, marginal zone and B1 B cells. Nat. Immunol. 4 (2003), 857–865.
135. Yin, L., Wu, L., Wesche, H., Arthur, C.D., White, J.M., Goeddel, D.V., Schreiber, R.D., Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Science 291 (2001), 2162–2165.
136. Young, R.M., Shaffer, A.L. 3rd, Phelan, J.D., Staudt, L.M., B-cell receptor signaling in diffuse large B-cell lymphoma. Semin. Hematol. 52 (2015), 77–85.
137. Yu, J.W., Hoffman, S., Beal, A.M., Dykon, A., Ringenberg, M.A., Hughes, A.C., Dare, L., Anderson, A.D., Finger, J., Kasparcova, V., et al. MALT1 Protease Activity Is Required for Innate and Adaptive Immune Responses. PLoS ONE, 10, 2015, e0127083.
138. Zhang, J., Stirling, B., Temmerman, S.T., Ma, C.A., Fuss, I.J., Derry, J.M., Jain, A., Impaired regulation of NF-kappaB and increased susceptibility to colitis-associated tumorigenesis in CYLD-deficient mice. J. Clin. Invest. 116 (2006), 3042–3049.
139. Zhou, Q., Wang, H., Schwartz, D.M., Stoffels, M., Park, Y.H., Zhang, Y., Yang, D., Demirkaya, E., Takeuchi, M., Tsai, W.L., et al. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat. Genet. 48 (2016), 67–73.
140. Zong, M., Wu, X.G., Chan, C.W., Choi, M.Y., Chan, H.C., Tanner, J.A., Yu, S., The adaptor function of TRAPPC2 in mammalian TRAPPs explains TRAPPC2-associated SEDT and TRAPPC9-associated congenital intellectual disability. PLoS ONE, 6, 2011, e23350.