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Physiological Roles and Mechanisms of Signaling by TRAF2 and TRAF5

  • Chapter
TNF Receptor Associated Factors (TRAFs)

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 597))

Abstract

TRAF2 and TRAF5 are closely related members of the TRAF family of proteins. They are important signal transducers for a wide range of TNF receptor superfamily members, including TNFR1, TNFR2, CD40 and other lymphocyte costimulatory receptors, RANK/TRANCE-R, EDAR, LTβR, LMP-1 and IRE1. TRAF2 and TRAF5 therefore regulate diverse physiological roles, ranging from T and B cell signaling and inflammatory responses to organogenesis and cell survival. The major pathways mediated by TRAF2 and TRAF5 are the classical and alternative pathways of NF-κB activation, and MAPK and JNK activation. TRAF2 is heavily regulated by ubiquitin signals, and many of the signaling functions of TRAF2 are mediated through its RING domain and likely its own role as an E3 ubiquitin ligase.

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References

  1. Rothe M, Wong SC, Henzel WJ et al. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 1994; 78(4):681–692.

    PubMed  CAS  Google Scholar 

  2. Ishida TK, Tojo T, Aoki T et al. TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling. Proc Natl Acad Sci USA 1996; 93(18):9437–9442.

    PubMed  CAS  Google Scholar 

  3. Nakano H, Oshima H, Chung W et al. TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor. J Biol Chem 1996; 271(25):14661–14664.

    PubMed  CAS  Google Scholar 

  4. Cao Z, Xiong J, Takeuchi M et al. TRAF6 is a signal transducer for interleukin-1. Nature 1996; 383(6599):443–446.

    PubMed  CAS  Google Scholar 

  5. Pullen SS, Miller HG, Everdeen DS et al. CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: Regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization. Biochemistry 1998; 37(34):11836–11845.

    PubMed  CAS  Google Scholar 

  6. Yeh WC, Shahinian A, Speiser D et al. Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity 1997; 7(5):715–725.

    PubMed  CAS  Google Scholar 

  7. Nakano H, Sakon S, Koseki H et al. Targeted disruption of Traf5 gene causes defects in CD40-and CD27-mediated lymphocyte activation. Proc Natl Acad Sci USA 1999; 96(17):9803–9808.

    PubMed  CAS  Google Scholar 

  8. Tada K, Okazaki T, Sakon S et al. Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death. J Biol Chem 2001; 276(39):36530–36534.

    PubMed  CAS  Google Scholar 

  9. Takaesu G, Surabhi RM, Park KJ et al. TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway. J Mol Biol 2003; 326(1):105–115.

    PubMed  CAS  Google Scholar 

  10. Rudolph D, Yeh WC, Wakeham A et al. Severe liver degeneration and lack of NF-kappaB activation in NEMO/IKKgamma-deficient mice. Genes Dev 2000; 14(7):854–862.

    PubMed  CAS  Google Scholar 

  11. Devin A, Lin Y, Yamaoka S et al. The alpha and beta subunits of IkappaB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF. Mol Cell Biol 2001; 21(12):3986–3994.

    PubMed  CAS  Google Scholar 

  12. Li Q, Van Antwerp D, Mercurio F et al. Severe liver degeneration in mice lacking the IkappaB kinase 2 gene. Science 1999; 284(5412):321–325.

    PubMed  CAS  Google Scholar 

  13. Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 1996; 274(5288):782–784.

    PubMed  CAS  Google Scholar 

  14. Van Antwerp DJ, Martin SJ, Kafri T et al. Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science 1996; 274(5288):787–789.

    PubMed  Google Scholar 

  15. Habelhah H, Takahashi S, Cho SG et al. Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-kappaB. EMBO J 2004; 23(2):322–332.

    PubMed  CAS  Google Scholar 

  16. Takeuchi M, Rothe M, Goeddel DV. Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins. J Biol Chem 1996; 271(33):19935–19942.

    PubMed  CAS  Google Scholar 

  17. Lee TH, Shank J, Cusson N et al. 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 2004; 279(32):33185–33191.

    PubMed  CAS  Google Scholar 

  18. Song HY, Rothe M, Goeddel DV. The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. Proc Natl Acad Sci USA 1996; 93(13):6721–6725.

    PubMed  CAS  Google Scholar 

  19. Wertz IE, O’Rourke KM, Zhou H. et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 2004; 430(7000):694–699.

    PubMed  CAS  Google Scholar 

  20. Devin A, Cook A, Lin Y et al. The distinct roles of TRAF2 and RIP in IKK activation. Immunity 2000; 12(4):419–429.

    PubMed  CAS  Google Scholar 

  21. Pomerantz JL, Baltimore D. NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO J 1999; 18(23):6694–6704

    PubMed  CAS  Google Scholar 

  22. Bonnard M, Mirtsos C, Suzuki S et al. Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription. EMBO J 2000; 19(18):4976–4985.

    PubMed  CAS  Google Scholar 

  23. Ramakrishnan P, Wang W, Wallach D. Receptor-specific signaling for both the alternative and the canonical NF-kappaB activation pathways by NF-kappaB-inducing kinase. Immunity 2004; 21(4):477–489.

    PubMed  CAS  Google Scholar 

  24. Lin X, Mu Y, Cunningham Jr ET et al. Molecular determinants of NF-kappaB-inducing kinase action. Mol Cell Biol 1998; 18(10):5899–5907.

    PubMed  CAS  Google Scholar 

  25. Grech AP, Amesbury M, Chan T et al. TRAF2 differentially regulates the canonical and noncanonical pathways of NF-kappaB activation in mature B cells. Immunity 2004; 21(5):629–642.

    PubMed  CAS  Google Scholar 

  26. Dobrzanski P, Ryseck RP, Bravo R. Differential interactions of Rel-NF-kappa B complexes with I kappa B alpha determine pools of constitutive and inducible NF-kappa B activity. EMBO J 1994; 13(19):4608–4616.

    PubMed  CAS  Google Scholar 

  27. Coope HJ, Atkinson PG, Huhse B et al. CD40 regulates the processing of NF-kappaB2 p100 to p52. EMBO J 2002; 21(20):5375–5385.

    PubMed  CAS  Google Scholar 

  28. Hauer J, Puschner S, Ramakrishnan P et al. TNF receptor (TNFR)-associated factor (TRAF) 3 serves as an inhibitor of TRAF2/5-mediated activation of the noncanonical NF-kappaB pathway by TRAF-binding TNFRs. Proc Natl Acad Sci USA 2005; 102(8):2874–2879.

    PubMed  CAS  Google Scholar 

  29. Hostager BS, Haxhinasto SA, Rowland SL et al. Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling. J Biol Chem 2003; 278(46):45382–45390.

    PubMed  CAS  Google Scholar 

  30. Baud V, Liu ZG, Bennett B et al. Signaling by proinflammatory cytokines: Oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev 1999; 13(10):1297–1308.

    PubMed  CAS  Google Scholar 

  31. Hoeflich KP, Yeh WC, Yao Z et al. Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating, kinase-1 (ASK1). Oncogene 1999; 18(42):5814–5820.

    PubMed  CAS  Google Scholar 

  32. Yuasa T, Ohno S, Kehrl JH et al. Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase upstream of MKK6 and p38. J Biol Chem 1998; 273(35):22681–22692.

    PubMed  CAS  Google Scholar 

  33. Shi CS, Leonardi A, Kyriakis J et al. TNF-mediated activation of the stress-activated protein kinase pathway: TNF receptor-associated factor 2 recruits and activates germinal center kinase related. J Immunol 1999; 163(6):3279–3285.

    PubMed  CAS  Google Scholar 

  34. Shi CS, Kehrl JH. 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 2003; 278(17):15429–15434.

    PubMed  CAS  Google Scholar 

  35. Legler DF, Micheau O, Doucey MA et al. Recruitment of TNF receptor 1 to lipid rafts is essential for TNFalpha-mediated NF-kappaB activation. Immunity 2003; 18(5):655–664.

    PubMed  CAS  Google Scholar 

  36. Wu CJ, Conze DB, Li X et al. TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination. EMBO J 2005; 24(10):1886–1898.

    PubMed  CAS  Google Scholar 

  37. Li X, Yang Y, Ashwell JD. TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 2002; 416(6878):345–347.

    PubMed  Google Scholar 

  38. Habelhah H, Frew IJ, Laine A et al. Stress-induced decrease in TRAF2 stability is mediated by Siah2. EMBO J 2002; 21(21):5756–5765.

    PubMed  CAS  Google Scholar 

  39. Kovalenko A, Chable-Bessia C, Cantarella G et al. The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature 2003; 424(6950):801–805.

    PubMed  CAS  Google Scholar 

  40. Brummelkamp TR, Nijman SM, Dirac AM et al. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature 2003; 424(6950):797–801.

    PubMed  CAS  Google Scholar 

  41. Trompouki E, Hatzivassiliou E, Tsichritzis T et al. CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. Nature 2003; 424(6950):793–796.

    PubMed  CAS  Google Scholar 

  42. Brown KD, Hostager BS, Bishop GA. Regulation of TRAF2 signaling by self-induced degradation. J Biol Chem 2002; 277(22):19433–19438.

    PubMed  CAS  Google Scholar 

  43. Hsu H, Shu HB, Pan MG et al. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 1996; 84(2):299–308.

    PubMed  CAS  Google Scholar 

  44. Muzio M, Salvesen GS, Dixit VM. FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens. J Biol Chem 1997; 272(5):2952–2956.

    PubMed  CAS  Google Scholar 

  45. Varfolomeev EE, Schuchmann M, Luria V et al. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apol, and DR3 and is lethal prenatally. Immunity 1998; 9(2):267–276.

    PubMed  CAS  Google Scholar 

  46. Hsu H, Xiong J, Goeddel DV. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 1995; 81(4):495–504.

    PubMed  CAS  Google Scholar 

  47. Yeh WC, Pompa JL, McCurrach ME et al. FADD: Essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science 1998; 279(5358):1954–1958.

    PubMed  CAS  Google Scholar 

  48. Park YC, Ye H, Hsia C et al. A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Cell 2000; 101(7):777–787.

    PubMed  CAS  Google Scholar 

  49. Hsu H, Huang J, Shu HB et al. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity 1996; 4(4):387–396.

    PubMed  CAS  Google Scholar 

  50. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003; 114(2):181–190.

    PubMed  CAS  Google Scholar 

  51. Nguyen LT, Duncan GS, Mirtsos C et al. TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses. Immunity 1999; 11(3):379–389.

    PubMed  CAS  Google Scholar 

  52. Kelliher MA, Grimm S, Ishida Y et al. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity 1998; 8(3):297–303.

    PubMed  CAS  Google Scholar 

  53. Lee SY, Reichlin A, Santana A et al. TRAF2 is essential for JNK but not NF-kappaB activation and regulates lymphocyte proliferation and survival. Immunity 1997; 7(5):703–713.

    PubMed  CAS  Google Scholar 

  54. Rothe M, Sarma V, Dixit VM et al. TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science 1995; 269(5229):1424–1427.

    PubMed  CAS  Google Scholar 

  55. Sakon S, Xue X, Takekawa M et al. NF-kappaB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J 2003; 22(15):3898–3909.

    PubMed  CAS  Google Scholar 

  56. Uren AG, Pakusch M, Hawkins CJ et al. Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc Natl Acad Sci USA 1996; 93(10):4974–4978.

    PubMed  CAS  Google Scholar 

  57. Wang CY, Mayo MW, Korneluk RG et al. NF-kappaB antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 1998; 281(5383):1680–1683.

    PubMed  CAS  Google Scholar 

  58. Tsitsikov EN, Laouini D, Dunn IF et al. TRAF1 is a negative regulator of TNF signaling. Enhanced TNF signaling in TRAF1-deficient mice. Immunity 2001; 15(4):647–657.

    PubMed  CAS  Google Scholar 

  59. Reinhard C, Shamoon B, Shyamala V et al. Tumor necrosis factor alpha-induced activation of c-jun N-terminal kinase is mediated by TRAF2. EMBO J 1997; 16(5):1080–1092.

    PubMed  CAS  Google Scholar 

  60. Jupp OJ, McFarlane SM, Anderson HM et al. Type II tumour necrosis factor-alpha receptor (TNFR2) activates c-Jun N-terminal kinase (JNK) but not mitogen-activated protein kinase (MAPK) or p38 MAPK pathways. Biochem J 2001; 359(Pt 3):525–535.

    PubMed  CAS  Google Scholar 

  61. Rothe M, Pan MG, Henzel WJ et al. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 1995; 83(7):1243–1252.

    PubMed  CAS  Google Scholar 

  62. Noelle RJ, Roy M, Shepherd DM et al. A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells. Proc Natl Acad Sci USA 1992; 89(14):6550–6554.

    PubMed  CAS  Google Scholar 

  63. Laman JD, Claassen E, Noelle RJ. Functions of CD40 and its ligand, gp39 (CD40L). Crit Rev Immunol 1996; 16(1):59–108.

    PubMed  CAS  Google Scholar 

  64. Pullen SS, Labadia ME, Ingraham RH et al. High-affinity interactions of tumor necrosis factor receptor-associated factors (TRAFs) and CD40 require TRAF trimerization and CD40 multimerization. Biochemistry 1999; 38(31):10168–10177.

    PubMed  CAS  Google Scholar 

  65. Haxhinasto SA, Hostager BS, Bishop GA. Cutting edge: Molecular mechanisms of synergy between CD40 and the B cell antigen receptor: Role for TNF receptor-associated factor 2 in receptor interaction. J Immunol 2002; 169(3):1145–1149.

    PubMed  CAS  Google Scholar 

  66. Haxhinasto SA, Bishop GA. A novel interaction between protein kinase D and TNF receptor-associated factor molecules regulates B cell receptor-CD40 synergy. J Immunol 2003; 171(9):4655–4662.

    PubMed  CAS  Google Scholar 

  67. Xia XZ, Treanor J, Senaldi G et al. TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation. J Exp Med 2000; 192(1):137–143.

    PubMed  CAS  Google Scholar 

  68. Hatzoglou A, Roussel J, Bourgeade MF et al. TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. J Immunol 2000; 165(3):1322–1330.

    PubMed  CAS  Google Scholar 

  69. Schiemann B, Gommerman JL, Vora K et al. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science 2001; 293(5537):2111–2114.

    PubMed  CAS  Google Scholar 

  70. Xu S, Lam KP. B-cell maturation protein, which binds the tumor necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses. Mol Cell Biol 2001; 21(12):4067–4047.

    PubMed  CAS  Google Scholar 

  71. Yan M, Wang, H, Chan B et al. Activation and accumulation of B cells in TACI-deficient mice. Nat Immunol 2001; 2(7):638–643.

    PubMed  CAS  Google Scholar 

  72. Thompson JS, Bixler SA, Qian F et al. BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science 2001; 293(5537):2108–2111.

    PubMed  CAS  Google Scholar 

  73. Watts TH. TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 2005; 23:23–68.

    PubMed  CAS  Google Scholar 

  74. Aizawa S, Nakano H, Ishida T et al. Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation. J Biol Chem 1997; 272(4):2042–2045.

    PubMed  CAS  Google Scholar 

  75. Duckett CS, Gedrich RW, Gilfillan MC et al. Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol Cell Biol 1997; 17(3):1535–1542.

    PubMed  CAS  Google Scholar 

  76. Wendtner CM, Schmitt B, Gruss HJ et al. CD30 ligand signal transduction involves activation of a tyrosine kinase and of mitogen-activated protein kinase in a Hodgkin’s lymphoma cell line. Cancer Res 1995; 55(18):4157–4161.

    PubMed  CAS  Google Scholar 

  77. Boucher LM, Marengere LE, Lu Y et al. Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily. Biochem Biophys Res Commun 1997; 233(3):592–600.

    PubMed  CAS  Google Scholar 

  78. Lee SY, Kandala G, Liou ML et al. CD30/TNF receptor-associated factor interaction: NF-kappa B activation and binding specificity. Proc Natl Acad Sci USA 1996; 93(18):9699–9703.

    PubMed  CAS  Google Scholar 

  79. Akiba H, Nakano H, Nishinaka S et al. CD27, a member of, the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase. J Biol Chem 1998; 273(21):13353–13358.

    PubMed  CAS  Google Scholar 

  80. Gravestein LA, Amsen D, Boes M et al. The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2. Eur J Immunol 1998; 28(7):2208–2216.

    PubMed  CAS  Google Scholar 

  81. Arch RH, Thompson CB. 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB. Mol Cell Biol 1998; 18(1):558–565.

    PubMed  CAS  Google Scholar 

  82. Kawamata S, Hori T, Imura A et al. Activation of OX40 signal transduction pathways leads to tumor necrosis factor receptor-associated factor (TRAF) 2-and TRAF5-mediated NF-kappaB activation. J Biol Chem 1998; 273(10):5808–5814.

    PubMed  CAS  Google Scholar 

  83. Prell RA, Evans DE, Thalhofer C et al. OX40-mediated memory T cell generation is TNF receptor-associated factor 2 dependent. J Immunol 2003; 171(11): 5997–6005.

    PubMed  CAS  Google Scholar 

  84. So T, Salek-Ardakani S, Nakano H et al. TNF receptor-associated factor 5 limits the induction of Th2 immune responses. J Immunol 2004; 172(7):4292–4297.

    PubMed  CAS  Google Scholar 

  85. Jang IK, Lee ZH, Kim YJ et al. Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B. Biochem Biophys Res Commun 1998; 242(3):613–620.

    PubMed  CAS  Google Scholar 

  86. Saoulli K, Lee SY, Cannons JL et al. CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand. J Exp Med 1998; 187(11):1849–1862.

    PubMed  CAS  Google Scholar 

  87. Cannons JL, Hoeflich KP, Woodgett JR et al. Role of the stress kinase pathway in signaling via the T cell costimulatory receptor 4-1BB. J Immunol 1999; 163(6):2990–2998.

    PubMed  CAS  Google Scholar 

  88. Cannons JL, Choi Y, Watts TH. Role of TNF receptor-associated factor 2 and p38 mitogen-activated protein kinase activation during 4-1BB-dependent immune response. J Immunol 2000; 165(11):6193–6204.

    PubMed  CAS  Google Scholar 

  89. Schneider K, Potter KG, Ware CF. Lymphotoxin and LIGHT signaling pathways and target genes. Immunol Rev 2004; 202:49–66.

    PubMed  CAS  Google Scholar 

  90. Kim YS, Nedospasov SA, Liu ZG. TRAF2 plays a key, nonredundant role in LIGHT-lymphotoxin beta receptor signaling. Mol Cell Biol 2005; 25(6):2130–2137.

    PubMed  CAS  Google Scholar 

  91. Force WR, Cheung TC, Ware CF. Dominant negative mutants of TRAF3 reveal an important role for the coiled coil domains in cell death signaling by the lymphotoxin-beta receptor. J Biol Chem 1997; 272(49):30835–30840.

    PubMed  CAS  Google Scholar 

  92. Kuai J, Nickbarg E, Wooters J et al. Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta recetor reveals a novel mechanism of apoptosis. J Biol Chem 2003; 278(16):14363–14369.

    PubMed  CAS  Google Scholar 

  93. Dejardin E, Droin NM, Delhase M et al. The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 2002; 17(4);525–535.

    PubMed  CAS  Google Scholar 

  94. Derudder E, Dejardin E, Pritchard LL et al. RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: Critical roles for p100. J Biol Chem 2003; 278(26):23278–23284.

    PubMed  CAS  Google Scholar 

  95. Koni PA, Sacca R, Lawton P et al. Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity 1997; 6(4):491–500.

    PubMed  CAS  Google Scholar 

  96. Futterer A, Mink K, Luz A et al. The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity 1998; 9(1):59–70.

    PubMed  CAS  Google Scholar 

  97. Caamano JH, Rizzo CA, Durham SK et al. Nuclear factor (NF)-kappa B2 (p100/p52) is required for normal splenic microarchitecture and B cell-mediated immune responses. J Exp Med 1998; 187(2):185–196.

    PubMed  CAS  Google Scholar 

  98. Hsu H, Solovyev I, Colombero A et al. ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5. J Biol Chem 1997; 272(21):13471–13474.

    PubMed  CAS  Google Scholar 

  99. Marsters SA, Ayres TM, Skubatch M et al. Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1. J Biol Chem 1997; 272(22):14029–14032.

    PubMed  CAS  Google Scholar 

  100. Wong BR, Josien R, Lee SY et al TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J Exp Med 1997; 186(12):2075–2080.

    PubMed  CAS  Google Scholar 

  101. Walsh MC, Choi Y. Biology of the TRANCE axis. Cytokine Growth Factor Rev 2003; 14(3–4):251–263.

    PubMed  CAS  Google Scholar 

  102. Darnay BG, Haridas V, Ni J et al. Characterization of the intracellular domain of receptor activator of NF-kappaB (RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappab and c-Jun N-terminal kinase. J Biol Chem 1998; 273(32):20551–20555.

    PubMed  CAS  Google Scholar 

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  1. Campbell Family for Breast Cancer Research, University Health Network and Department of Medical Biophysics, University of Toronto, Toranto, Ontario, M5G 2C1

    Wen-Chen Yeh

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  1. Ping-Yee Billie Au
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  1. Department of Biochemistry, Weill Medical College of Cornell University, New York, New York, USA

    Hao Wu Ph.D.

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Au, PY.B., Yeh, WC. (2007). Physiological Roles and Mechanisms of Signaling by TRAF2 and TRAF5. In: Wu, H. (eds) TNF Receptor Associated Factors (TRAFs). Advances in Experimental Medicine and Biology, vol 597. Springer, New York, NY. https://doi.org/10.1007/978-0-387-70630-6_3

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