채성원 Table 1. NF-B and IKK proteins Protein Other names NF-B proteins p50 p105 NF-B1, p110, KBF1, EBO-1 p52 p100 NF-B2, p50b, p49, p55, Lyt10, H2TF1 Re

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1 KISEP Information Korean J Otolaryngol 2005;48:284-8 NF-κB의 활성화와 면역학적 기능 채 성 원 Function and Activation of NF-κB in Immune System Sung Won Chae, MD, PhD Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea

Chae, MD, PhD Department of Otorhinolaryngology-Head and Neck Surgery,

2 채성원 Table 1. NF-B and IKK proteins Protein Other names NF-B proteins p50 p105 NF-B1, p110, KBF1, EBO-1 p52 p100 NF-B2, p50b, p49, p55, Lyt10, H2TF1 RelA p65 I-Rel IB kinase IKK proteins IKK IKK1, CHUK IKK IKK2 IKK IKK3, NEMO NF-B essential modulator Viruses TLRs Cytokines Proinflmmatory Antigen cytokines receptors LTR, BAFF, CD40L IKK IKK IKK IB p50 p65 p50 p65 mrna IKK IKK p52 NIK p100 mrna proteins proteins GGG Ankyrin repeats p52 Target genes GGG p50 V- Rel RelA p65 Innate immunity Inflammation Cell survival Fig. 2. Classical and alternative NF-κB pathway. AThe classical NF-κB pathway is activated by a variety of inflammatory signals. BThe alternative NF-κB pathway is strictly dependent on IKKα homodimers and is activated by NIK. IKKIκB kinase, NIKNFκB-inducing kinase, LTlymphotoxin, BAFFB-cell activating factor belong to the TNFG family, CD40LCD40 ligand. L Z C-Rel Fig. 1. NF-κB proteins contain a well conserved Rel-homology domain. Some proteins, such as c-rel, and RelA, contain transactivation domains in addition to the

IKK IKK3, NEMO NF-B essential modulator Viruses TLRs Cytokines Proinflmmatory Antigen cytokines receptors LTR, BAFF, CD40L IKK IKK IKK IB p50 p65 p50 p65 mrna IKK IKK p52 NIK p100 mrna proteins

3 NF-B의 면역학적 기능 Korean J Otolaryngol 2005;48:284-8

4 채성원

5 NF-B의 면역학적 기능 - REFERENCES 1) Yamamoto Y, Gaynor RB. Ikappab kinases: Key regulators of the NFκB pathway. Trends Biochem Sci 2004;29: ) Bonizzi G, Karin M. The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004;25: ) Mercurio F, DiDonato JA, Rosette C, Karin M. P105 and p98 precursor proteins play an active role in NF-κB -mediated signal transduction. Genes Dev 1993;7: ) Alcamo E, Mizgerd JP, Horwitz BH, Bronson R, Beg AA, Scott M, et al. Targeted mutation of TNF receptor 1 rescues the RelA-deficient mouse and reveals a critical role for NF-κB in leukocyte recruitment. J Immunol 2001;167: ) Elewaut D, DiDonato JA, Kim JM, Truong F, Eckmann L, Kagnoff MF. NF-κB is a central regulator of the intestinal epithelial cell innate immune response induced by infection with enteroinvasive bacteria. J Immunol 1999;163: ) Claudio E, Brown K, Park S, Wang H, Siebenlist U. BAFF-induced NEMO-independent processing of NF-κB 2 in maturing B cells. Nat Immunol 2002;3: ) Li Q, Estepa G, Memet S, Israel A,Verma IM. Complete lack of NFκB activity in IKK1 and IKK2 double-deficient mice: Additional defect in neurulation. Genes Dev 2000;14: ) Muller JR, Siebenlist U. Lymphotoxin beta receptor induces sequential activation of distinct NF-κB factors via separate signaling pathways. J Biol Chem 2003;278: ) Zandi E, Chen Y, Karin M. Direct phosphorylation of Ikappab by IKKalpha and IKKbeta: Discrimination between free and NF-κBbound substrate. Science 1998;281: ) Takeda K, Takeuchi O, Tsujimura T, Itami S, Adachi O, Kawai T, et al. Limb and skin abnormalities in mice lacking IKKalpha. Science 1999;284: ) Cao Y, Bonizzi G, Seagroves TN, Greten FR, Johnson R, Schmidt EV, et al. IKKalpha provides an essential link between rank signaling and cyclin D1 expression during mammary gland development. Cell 2001; 107: ) Silverman N, Zhou R, Stoven S, Pandey N, Hultmark D, Maniatis T. A drosophila IKK complex required for relish cleavage and antibacterial immunity. Genes Dev 2000;14: ) Ghosh S, May MJ, Kopp EB. NF-κB and Rel proteins: Evolutionarily conserved mediators of immune responses. Annu Rev Immunol 1998;16: ) Wickremasinghe MI, Thomas LH, Friedland JS. Pulmonary epithelial cells are a source of IL-8 in the response to mycobacterium tuberculosis: Essential role of IL-1 from infected monocytes in a NF-κBdependent network. J Immunol 1999;163: ) Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol 2001;1: ) Gewirtz AT, Navas TA, Lyons S, Godowski PJ, Madara JL. Cutting edge: Bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J Immunol 2001; 167: ) Grigoriadis G, Zhan Y, Grumont RJ, Metcalf D, Handman E, Cheers C, et al. The Rel subunit of NF-κB-like transcription factors is a positive and negative regulator of macrophage gene expression: Distinct roles for Rel in different macrophage populations. Embo J 1996;15: ) Weih F, Carrasco D, Bravo R. Constitutive and inducible Rel/NF-κB activities in mouse thymus and spleen. Oncogene 1994;9: ) Karin M, Lin A. NF-κB at the crossroads of life and death. Nat Immunol 2002;3: ) Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, et al. IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. Embo J 1998;17: ) Tomlinson A, Appleton I, Moore AR, Gilroy DW, Willis D, Mitchell JA, et al. Cyclo-oxygenase and nitric oxide synthase isoforms in rat carrageenin-induced pleurisy. Br J Pharmacol 1994;113: ) Lawrence T, Gilroy DW, Colville-Nash PR, Willoughby DA. Possible new role for NF-κB in the resolution of inflammation. Nat Med 2001; 7: ) Gilmore T, Gapuzan ME, Kalaitzidis D, Starczynowski D. Rel NF-κB/ IκB signal transduction in the generation and treatment of human cancer. Cancer Lett 2002;181: ) Duyao MP, Kessler DJ, Spicer DB, Bartholomew C, Cleveland JL, Siekevitz M, et al. Transactivation of the c-myc promoter by human T cell leukemia virus type 1 tax is mediated by NF-κB. J Biol Chem 1992;267: ) Li N, Karin M. Ionizing radiation and short wavelength uv activate NF-κB through two distinct mechanisms. Proc Natl Acad Sci USA 1998;95: Korean J Otolaryngol 2005;48:284-8

P105 and p98 precursor proteins play an active role in NF-κB -mediated signal transduction. Genes Dev 1993;7:705-18. 4) Alcamo E, Mizgerd JP, Horwitz BH, Bronson R, Beg AA, Scott M, et al.

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