Phylogeny of the TRAF/MATH Domain

  • Juan M. Zapata
  • Vanesa Martínez-García
  • Sophie Lefebvre
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 597)


The TNF-receptor associated factor (TRAF) domain (TD), also known as the meprin and TRAF-C homology (MATH) domain is a fold of seven anti-parallel ß-helices that participates in protein-protein interactions. This fold is broadly represented among eukaryotes, where it is found associated with a discrete set of protein-domains. Virtually all protein families encompassing a TRAF/MATH domain seem to be involved in the regulation of protein processing and ubiquitination, strongly suggesting a parallel evolution of the TRAF/MATH domain and certain proteolysis pathways in eukaryotes.

The restricted number of living organisms for which we have information of their genetic and protein make-up limits the scope and analysis of the MATH domain in evolution. However, the available information allows us to get a glimpse on the origins, distribution and evolution of the TRAF/MATH domain, which will be overviewed in this chapter.


Latent Membrane Protein Zinc Finger Domain Ring Finger Domain TNFR Family Conserve Domain Architecture Retrieval Tool 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Chung JY, Park YC, Ye H et al. All TRAFs are not created equal: Common and distinct molecular mechanisms of TRAF-mediated signal transduction. J Cell Sci 2002; 115:679–688.PubMedGoogle Scholar
  2. 2.
    Zapata JM. TNF-receptor-associated factors as targets for drug development. Expert Opin Ther Targets 2003; 7(3):411–425.PubMedCrossRefGoogle Scholar
  3. 3.
    Bradley JR, Pober JS. Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene 2001; 20:6482–6491.PubMedCrossRefGoogle Scholar
  4. 4.
    Bishop GA. The multifaceted roles of TRAFs in the regulation of B-cell function. Nat Rev Immunol 2004; 4(10):775–786.PubMedCrossRefGoogle Scholar
  5. 5.
    Uren AG, Vaux DL. TRAF proteins and meprins share a conserved domain. Trends Biochem Sci 1996; 21(7):244–245.PubMedCrossRefGoogle Scholar
  6. 6.
    Sunnerhagen M, Pursglove S, Fladvad M. The new MATH: Homology suggests shared binding surfaces in meprin tetramers and TRAF trimers. FEBS Lett 2002; 530(1–3):1–3.PubMedCrossRefGoogle Scholar
  7. 7.
    Zapata JM, Pawlowski K, Haas E et al. A diverse family of proteins containing Tumor Necrosis Factor Receptor-associated Factor domains. J Biol Chem 2001; 276:24242–24252.PubMedCrossRefGoogle Scholar
  8. 8.
    Amerik AY, Hochstrasser M. Mechanism and function of deubiquitinating enzymes. Biochim Biophys Acta 2004; 1695(1–3):189–207.PubMedGoogle Scholar
  9. 9.
    Nijman SM, Luna-Vargas MP, Velds A et al. A genomic and functional inventory of deubiquitinating enzymes. Cell 2005; 123(5):773–786.PubMedCrossRefGoogle Scholar
  10. 10.
    Semple CA. The comparative proteomics of ubiquitination in mouse. Genome Res 2003; 13(6B):1389–1394.PubMedCrossRefGoogle Scholar
  11. 11.
    Saridakis V, Sheng Y, Sarkari F et al. Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization. Mol Cell 2005; 18(1):25–36.PubMedCrossRefGoogle Scholar
  12. 12.
    Everett R, Meredith M, Orr A et al. A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO J 1997; 16:566–577.PubMedCrossRefGoogle Scholar
  13. 13.
    Sheng Y, Saridakis V, Sarkari F et al. Molecular recognition of p53 and MDM2 by USP7/HAUSP. Nat Struct Mol Biol 2006; 13(3):285–291.PubMedCrossRefGoogle Scholar
  14. 14.
    Ye H, Park Y, Kreishman M et al. The structural basis for the recognition of diverse receptor sequences by TRAF2. Mol Cell 1999; 4:321–330.PubMedCrossRefGoogle Scholar
  15. 15.
    Ni CZ, Welsh K, Leo E et al. Molecular basis for CD40 signaling mediated by Traf3. Proc Natl Acad Sci USA 2000; 97:10395–10399.PubMedCrossRefGoogle Scholar
  16. 16.
    McWhirter S, Pullen S, Holton J et al. Cristalographic analyses of CD40 recognition and signaling by human TRAF2. Proc Natl Acad Sci USA 1999; 96:8408–8413.PubMedCrossRefGoogle Scholar
  17. 17.
    Park Y, Burkitt V, Villa A et al. Structural basis for self-association and receptor recognition of human TRAF2. Nature 1999; 398:533–538.PubMedCrossRefGoogle Scholar
  18. 18.
    Hu M, Gu L, Li M et al. Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: Implications for the regulation of the p53-MDM2 pathway. PLoS Biol 2006; 4(2):e27.PubMedCrossRefGoogle Scholar
  19. 19.
    Li M, Brooks CL, Wu-Baer F et al. Mono-versus polyubiquitination: Differential control of p53 fate by Mdm2. Science 2003; 302(5652):1972–1975.PubMedCrossRefGoogle Scholar
  20. 20.
    Cummins JM, Rago C, Kohli M et al. Tumour suppression: Disruption of HAUSP gene stabilizes p53. Nature 2004; 428(6982):1, (following 486).PubMedCrossRefGoogle Scholar
  21. 21.
    Li M, Brooks CL, Kon N et al. A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol Cell 2004; 13(6):879–886.PubMedCrossRefGoogle Scholar
  22. 22.
    Li M, Chen D, Shiloh A et al. Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature 2002; 416:648–653.PubMedCrossRefGoogle Scholar
  23. 23.
    Raychaudhuri S, Niu L, Conrad J et al. Functional effect of deletion and mutation of the Escherichia coli ribosomal RNA and tRNA pseudouridine synthase RluA. J Biol Chem 1999; 274(27):18880–18886.PubMedCrossRefGoogle Scholar
  24. 24.
    Traub P, Mothes E, Shoeman R et al. Characterization of the nucleic acid-binding activities of the isolated amino-terminal head domain of the intermediate filament protein vimentin reveals its close relationship to the DNA-binding regions of some prokaryotic single-stranded DNA-binding proteins. J Mol Biol 1992; 228(1):41–57.PubMedCrossRefGoogle Scholar
  25. 25.
    Bardwell VJ, Treisman R. The POZ domain: A conserved protein-protein interaction motif. Genes Dev 1994; 8(14):1664–1677.PubMedCrossRefGoogle Scholar
  26. 26.
    Stogios PJ, Downs GS, Jauhal JJ et al. Sequence and structural analysis of BTB domain proteins. Genome Biol 2005; 6(10):R82.PubMedCrossRefGoogle Scholar
  27. 27.
    Ahmad KF, Engel CK, Prive GG. Crystal structure of the BTB domain from PLZF. Proc Natl Acad Sci USA 1998; 95(21):12123–12128.PubMedCrossRefGoogle Scholar
  28. 28.
    van den Heuvel S. Protein degradation: CUL-3 and BTB—partners in proteolysis Curr Biol 2004; 14(2):R59–61.PubMedCrossRefGoogle Scholar
  29. 29.
    Xu L, Wei Y, Reboul J et al. BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3. Nature 2003; 425(6955):316–321.PubMedCrossRefGoogle Scholar
  30. 30.
    Pintard L, Willis JH, Willems A et al. The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase. Nature 2003; 425(6955):311–316.PubMedCrossRefGoogle Scholar
  31. 31.
    Geyer R, Wee S, Anderson S et al. BTB/POZ domain proteins are putative substrate adaptors for cullin 3 ubiquitin ligases. Mol Cell 2003; 12(3):783–790.PubMedCrossRefGoogle Scholar
  32. 32.
    Nagai Y, Kojima T, Muro Y et al. Identification of a novel nuclear speckle-type protein, spop. FEBS Letters 1997; 418:23–26.PubMedCrossRefGoogle Scholar
  33. 33.
    Reed JC, Doctor K, Rojas A et al. Comparative analysis of apoptosis and inflammation genes of mice and humans. Genome Res 2003; 13(6B):1376–1388.PubMedCrossRefGoogle Scholar
  34. 34.
    Liu L, Andrews LG, Tollefsbol TO. Loss of the human polycomb group protein BMI1 promotes cancer-specific cell death. Oncogene 2006; (In press).Google Scholar
  35. 35.
    Valk-Lingbeek ME, Bruggeman SW, van Lohuizen M. Stem cells and cancer; the polycomb connection. Cell 2004; 118(4):409–418.PubMedCrossRefGoogle Scholar
  36. 36.
    Park IK, Morrison SJ, Clarke MF. Bmil, stem cells, and senescence regulation. J Clin Invest 2004; 113(2):175–179.PubMedCrossRefGoogle Scholar
  37. 37.
    Hernandez-Munoz I, Lund AH, van der Stoop P et al. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. Proc Natl Acad Sci USA 2005; 102(21):7635–7640.PubMedCrossRefGoogle Scholar
  38. 38.
    Kwon JE, La M, Oh KH et al. BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of DAXX for ubiquitination by Cul3-based ubiquitin ligase. J Biol Chem 2006.Google Scholar
  39. 39.
    Reymond A, Meroni G, Fantozzi A et al. The tripartite motif family identifies cell compartments. EMBO J 2001; 20(9):2140–2151.PubMedCrossRefGoogle Scholar
  40. 40.
    Avela K, Lipsanen-Nyman M, Idanheimo N et al Gene encoding a new RING-B-box coiled-coil protein is mutated in mulibrey nanism. Nat Genet 2000; 25:298–301.PubMedCrossRefGoogle Scholar
  41. 41.
    Lapunzina P, Rodriguez JI, de Matteo E. et al. Mulibrey nanism: Three additional patients and a review of 39 patients. Am J Med Genet 1995; 55:349–355.PubMedCrossRefGoogle Scholar
  42. 42.
    Lipsanen-Nyman M, Perheentupa J, Rapola J et al. Mulibrey heart disease: Clinical manifestations, long-term course, and results of pericardiectomy in a series of 49 patients born before 1985. Circulation 2003; 107(22):2810–2815.PubMedCrossRefGoogle Scholar
  43. 43.
    Karlberg S, Tiitinen A, Lipsanen-Nyman M. Failure of sexual maturation in Mulibrey, nanism. N Engl J Med 2004; 351(24):2559–2560.PubMedCrossRefGoogle Scholar
  44. 44.
    Meroni G, Diez-Roux G. TRIM/RBCC, a novel class of’ single protein RING finger’ E3 ubiquitin ligases. Bioessays 2005; 27(11):1147–1157.PubMedCrossRefGoogle Scholar
  45. 45.
    Kallijarvi, J, Avela K, Lipsanen-Nyman M et al. The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: Classification of mulibrey, nanism as a new peroxisomal disorder. Am J Hum Genet 2002: 70:1215–1228.PubMedCrossRefGoogle Scholar
  46. 46.
    Bond JS, Beynon RJ. The astacin family of metalloendopeptidases. Protein Sci 1995; 4:1247–1261.PubMedCrossRefGoogle Scholar
  47. 47.
    Villa JP, Bertenshaw GP, Bylander JE et al. Meprin proteolytic complexes at the cell surface and in extracellular spaces. Biochem Soc Symp 2003; (70):53–63.Google Scholar
  48. 48.
    Laine A, Ronai Z. Ubiquitin chains in the ladder of MAPK signaling. Sci STKE 2005; 2005(281):re5.PubMedCrossRefGoogle Scholar
  49. 49.
    Xu LG, Li LY, Shu HB. TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. J Biol Chem 2004; 279(17):17278–17282.PubMedCrossRefGoogle Scholar
  50. 50.
    Brown KD, Hostager BS, Bishop GA. Regulation of TRAF2 signaling by self-induced degradation. J Biol Chem 2002; 277(22):19433–19438.PubMedCrossRefGoogle Scholar
  51. 51.
    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.PubMedCrossRefGoogle Scholar
  52. 52.
    Liao G, Zhang M, Harhaj EW et al. Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem 2004; 279(25):26243–26250.PubMedCrossRefGoogle Scholar
  53. 53.
    Chen ZJ. Ubiquitin signalling in the NF-kappaB pathway. Nat Cell Biol 2005; 7(8):758–765.PubMedCrossRefGoogle Scholar
  54. 54.
    Liu H, Su YC, Becker E et al. A Drosophila TNF-receptor-associated factor (TRAF) binds the Ste20 kinase Misshapen and activates Jun kinase. Curr Biol 1999; 9:101–104PubMedCrossRefGoogle Scholar
  55. 55.
    Zapata JM, Matsuzawa S, Godzik A et al. The drosophila TNF-receptor associated factor-1 (DTRAF1) interacts with pelle and regulates NFkB activity. J Biol Chem 2000; 275:12102–12107.PubMedCrossRefGoogle Scholar
  56. 56.
    Shen B, Liu H, Skolnik EY et al. Physical and functional interactions between Drosophila TRAF2 and pelle kinase contribute to dorsal activation. Proc Natl Acad Sci USA 2001; 98:8596–8601.PubMedCrossRefGoogle Scholar
  57. 57.
    Muller WE, Muller IM. Analysis of the sponge [Porifera] gene repertoire: Implications for the evolution of the metazoan body plan. Prog Mol Subcell Biol 2003; 37:1–33.PubMedGoogle Scholar
  58. 58.
    Grech A, Quinn R, Srinivasan D et al. Complete structural characterisation of the mammalian and Drosophila TRAF genes: Implications for TRAF evolution and the role of RING finger splice variants. Mol Immunol 2000; 37(12–13):721–734.PubMedCrossRefGoogle Scholar
  59. 59.
    Eichinger L, Pachebat JA, Glockner G et al. The genome of the social amoeba Dictyostelium discoideum. Nature 2005; 435(7038):43–57.PubMedCrossRefGoogle Scholar
  60. 60.
    Kessin RH. Dictyostelium. Vol. 14. Cambridge: Cambridge University Press, 2001.Google Scholar
  61. 61.
    Mali B, Frank U. Hydroid TNF-receptor-associated factor (TRAF) and its splice variant: A role in development. Mol Immunol 2004; 41(4):377–384.PubMedCrossRefGoogle Scholar
  62. 62.
    Cha GH, Cho KS, Lee JH et al. Discrete functions of TRAF1 and TRAF2 in Drosophila melanogaster mediated by c-Jun N-terminal kinase and NF-kappaB-dependent signaling pathways. Mol Cell Biol 2003; 23(22):7982–7991.PubMedCrossRefGoogle Scholar
  63. 63.
    Kedinger V, Alpy F, Tomasetto C et al. Spatial and temporal distribution of the traf4 genes during zebrafish development. Gene Expr Patterns 2005; 5(4):545–552.PubMedGoogle Scholar
  64. 64.
    Regnier CH, Masson R, Kedinger V et al. Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice. Proc Natl Acad Sci USA 2002; 99(8):5585–5590.PubMedCrossRefGoogle Scholar
  65. 65.
    Xu YC, Wu RF, Gu Y et al. Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase. J Biol Chem 2002; 277(31):28051–28057.PubMedCrossRefGoogle Scholar
  66. 66.
    Abell AN, Johnson GL. MEKK4 is an effector of the embryonic TRAF4 for JNK activation. J Biol Chem 2005; 280(43):35793–35796.PubMedCrossRefGoogle Scholar
  67. 67.
    Chi H, Sarkisian MR, Rakic P et al. Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in enhanced apoptosis and defective neural tube development. Proc Natl Acad Sci USA 2005; 102(10):3846–3851.PubMedCrossRefGoogle Scholar
  68. 68.
    Abell AN, Rivera-Perez JA, Cuevas BD et al. Ablation of MEKK4 kinase activity causes neurulation and skeletal patterning defects in the mouse embryo. Mol Cell Biol 2005; 25(20):8948–8959.PubMedCrossRefGoogle Scholar
  69. 69.
    Kopp E, Medzhitov R, Carothers J et al. ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway. Genes Dev 1999; 13(16):2059–2071.PubMedGoogle Scholar
  70. 70.
    Janeway Jr CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002; 20:197–216.PubMedCrossRefGoogle Scholar
  71. 71.
    Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004; 5(10):987–995.PubMedCrossRefGoogle Scholar
  72. 72.
    Kaisho T, Akira S. Pleiotropic function of Toll-like receptors. Microbes Infect 2004; 6(15):1388–1394.PubMedCrossRefGoogle Scholar
  73. 73.
    Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006; 124(4):783–801.PubMedCrossRefGoogle Scholar
  74. 74.
    Royet J, Reichhart JM, Hoffmann JA. Sensing and signaling during infection in Drosophila. Curr Opin Immunol 2005; 17(1):11–17.PubMedCrossRefGoogle Scholar
  75. 75.
    Christophides GK, Zdobnov E, Barillas-Mury C et al. Immunity-related genes and gene families in Anopheles gambiae. Science 2002; 298(5591):159–165.PubMedCrossRefGoogle Scholar
  76. 76.
    Kimbrell DA, Beutler B. The evolution and genetics of innate immunity. Nature Rev 2001; 2:256–267.CrossRefGoogle Scholar
  77. 77.
    Brennan CA, Anderson KV. Drosophila: The genetics of innate immune recognition and response. Annu Rev Immunol 2004; 22:457–483.PubMedCrossRefGoogle Scholar
  78. 78.
    Deng L, Wang C, Spencer E et al. Activation of the IkB kinase complex TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 2000; 103:351–361.PubMedCrossRefGoogle Scholar
  79. 79.
    Jiang Z, Ninomiya-Tsuji J, Qian Y et al. Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol. Mol Cell Biol 2002; 22(20):7158–7167.PubMedCrossRefGoogle Scholar
  80. 80.
    Wang C, Deng L, Hong M et al. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 2001; 412:346–351.PubMedCrossRefGoogle Scholar
  81. 81.
    Zhou R, Silverman N, Hong M et al. The role of ubiquitination in Drosophila innate immunity. J Biol Chem 2005; 280(40):34048–34055.PubMedCrossRefGoogle Scholar
  82. 82.
    Cusson-Hermance N, Khurana S, Lee TH et al. Rip1 mediates the Trif-dependent toll-like receptor 3-and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation. J Biol Chem 2005; 280(44):36560–36566.PubMedCrossRefGoogle Scholar
  83. 83.
    Oganesyan G, Saha SK, Guo B et al. Critical role of TRAF3 in the Toll-like receptor-dependent and-independent antiviral response. Nature 2005; 439:208–211.PubMedCrossRefGoogle Scholar
  84. 84.
    Hacker H, Redecke V, Blagoev B et al. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature 2005; 439:204–207.PubMedCrossRefGoogle Scholar
  85. 85.
    Igaki T, Kanda H, Yamamoto-Goto Y et al. Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. EMBO J 2002; 21:3009–3018.PubMedCrossRefGoogle Scholar
  86. 86.
    Ye H, Arron JR, Lamothe B et al. Distinct molecular mechanism for initiating TRAF6 signalling. Nature 2002; 418:443–447.PubMedCrossRefGoogle Scholar
  87. 87.
    Ye X, Mehlen P, Rabizadeh S et al. TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction. J Biol Chem 1999; 274:30202–30208.PubMedCrossRefGoogle Scholar
  88. 88.
    Krajewska M, Krajewski S, Zapata JM et al. TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues. Amer J Pathol 1998; 152:1549–1561.Google Scholar
  89. 89.
    Esparza EM, Arch RH. TRAF4 functions as an intermediate of GITR-induced NF-kappaB activation. Cell Mol Life Sci 2004; 61(24):3087–3092.PubMedCrossRefGoogle Scholar
  90. 90.
    Zapata JM, Reed JC. TRAF1: Lord without a RING. Science STKE 2002, (; 2002/133/pe27n).
  91. 91.
    Zapata JM, Krajewska M, Morse IIIrd HC et al. TNF receptor-associated factor (TRAF) domain and Bcl-2 cooperate to induce small B cell lymphoma/chronic lymphocytic leukemia in transgenic mice. Proc Natl Acad Sci USA 2004; 101(47):16600–16605.PubMedCrossRefGoogle Scholar
  92. 92.
    Xie P, Hostager BS, Munroe ME et al. Cooperation between TNF receptor-associated factors 1 and 2 in CD40 signaling. J Immunol 2006; 176(9):5388–5400.PubMedGoogle Scholar
  93. 93.
    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-{kappa}B pathway by TRAF-binding TNFRs. Proc Natl Acad Sci USA 2005; 102(8):2874–2879.PubMedCrossRefGoogle Scholar
  94. 94.
    Naito A, Azuma S, Tanaka S et al. Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes to Cells 1999; 4:353–362.PubMedCrossRefGoogle Scholar
  95. 95.
    Lomaga M, Yeh WC, Sarosi I et al. TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 1999; 13:1015–1024.PubMedGoogle Scholar
  96. 96.
    Armstrong AP, Tometsko ME, Glaccum M et al. A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function. J Biol Chem 2002; 277(46):44347–44356.PubMedCrossRefGoogle Scholar
  97. 97.
    Mizukami J, Takaesu G, Akatsuka H et al. Receptor activator of NF-kappaB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containing RANK, TAB2, and TRAF6. Mol Cell Biol 2002; 22(4):992–1000.PubMedCrossRefGoogle Scholar
  98. 98.
    Naito A, Yoshida H, Nishioka E et al. TRAF6-deficient mice display hypohidrotic ectodermal dysplasia. Proc Natl Acad Sci USA 2002; 99(13):8766–8771.PubMedGoogle Scholar
  99. 99.
    Williams H, Crawford DH. Epstein-barr virus: Impact of scientific advance on clinical practice. Blood 2005; 107(3):862–869.PubMedCrossRefGoogle Scholar
  100. 100.
    Bishop GA, Hostager BS. Signaling by CD40 and its mimics in B cell activation. Immunol Res 2001; 24(2):97–109.PubMedCrossRefGoogle Scholar
  101. 101.
    Bishop GA, Busch LK. Molecular mechanisms of B-lymphocyte transformation by Epstein-Barr virus. Microbes Infect 2002; 4(8):853–857.PubMedCrossRefGoogle Scholar
  102. 102.
    Lam N, Sugden B. CD40 and its viral mimic, LMP1: Similar means to different ends. Cell Signal 2003; 15(1):9–16.PubMedCrossRefGoogle Scholar
  103. 103.
    Uchida J, Yasui T, Takaoka-Shichijo Y et al. Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses. Science 1999; 286(5438):300–303.PubMedCrossRefGoogle Scholar
  104. 104.
    Brown KD, Hostager BS, Bishop GA. Differential signaling and tumor necrosis factor receptor-associated factor (TRAF) degradation mediated by CD40 and the Epstein-Barr virus oncoprotein latent membrane protein 1 (LMP1). J Exp Med 2001; 193(8):943–954.PubMedCrossRefGoogle Scholar
  105. 105.
    Canning M, Boutell C, Parkinson J et al. A RING finger ubiquitin ligase is protected from autocatalyzed ubiquitination and degradation by binding to ubiquitin-specific protease USP7. J Biol Chem 2004; 279(37):38160–38168.PubMedCrossRefGoogle Scholar
  106. 106.
    Guasparri I, Wu H, Cesarman E. The KSHV oncoprotein vFLIP contains a TRAF-interacting motif and requires TRAF2 and TRAF3 for signalling. EMBO Rep 2006; 7(1):114–119.PubMedCrossRefGoogle Scholar
  107. 107.
    Thurau M, Everett H, Tapernoux M et al. The TRAF3-binding site of human molluscipox virus FLIP molecule MC159 is critical for its capacity to inhibit Fas-induced apoptosis. Cell Death Differ 2006; (In press).Google Scholar
  108. 108.
    Matsuzawa S, Reed JC. Siah-1, SIP, and Ebi collaborate in a novel pathway for ∖beta∖-catenin degradation linked to p53 responses. Mol Cell 2001; 7:915–926.PubMedCrossRefGoogle Scholar
  109. 109.
    Polekhina G, House CM, Traficante N et al. The siah ubiquitin ligase component is structurally related to the TRAF family of proteins and modulates TNF-∖alpha∖-signalling. Nature Struct Biol 2002; 9(1):68–75.PubMedCrossRefGoogle Scholar
  110. 110.
    Santelli E, Leone M, Li C et al. Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex. J Biol Chem 2005; 280(40):34278–34287.PubMedCrossRefGoogle Scholar
  111. 111.
    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.PubMedCrossRefGoogle Scholar
  112. 112.
    Jaroszewski L, Rychlewski B, Zhang B et al. Fold prediction by a hierarchy of sequence and threading methods. Protein Science 1998; 7:1431–1440.PubMedGoogle Scholar
  113. 113.
    Sali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 1993; 234:779–815.PubMedCrossRefGoogle Scholar
  114. 114.
    Marchler-Bauer A, Bryant SH. CD-Search: Protein domain annotations on the fly. Nucleic Acids Res 2004; 32(Web Server issue):W327–331.CrossRefGoogle Scholar
  115. 115.
    Marchler-Bauer A, Anderson JB, Cherukuri PF et al. CDD: A conserved domain database for protein classification. Nucleic Acids Res 2005; 33(Database issue):D192–196.PubMedCrossRefGoogle Scholar
  116. 116.
    Geer LY, Domrachev M, Lipman DJ et al. CDART: Protein homology by domain architecture. Genome Res 2002; 12(10):1619–1623.PubMedCrossRefGoogle Scholar
  117. 117.
    Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998; 67:425–479.PubMedCrossRefGoogle Scholar
  118. 118.
    Hochstrasser M. Evolution and function of ubiquitin-like protein-conjugation systems. Nat Cell Biol 2000; 2(8):E153–157.PubMedCrossRefGoogle Scholar
  119. 119.
    Edgar RC. MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 2004; 32(5):1792–1797.PubMedCrossRefGoogle Scholar
  120. 120.
    Edgar RC. MUSCLE: A multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 2004; 5:113.PubMedCrossRefGoogle Scholar
  121. 121.
    Eddy SR. Where did the BLOSUM62 alignment score matrix come from? Nat Biotechnol 2004; 22(8):1035–1036.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Juan M. Zapata
    • 1
    • 2
  • Vanesa Martínez-García
  • Sophie Lefebvre
  1. 1.Burnham Institute for Medical ResearchLa JollaUSA
  2. 2.Centro de Biología Molecular Severo OchoaUniversidad Autónoma de MadridMadridSpain

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