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Hodgkin’s Lymphoma and CD30 Signal Transduction

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Abstract

Advances in molecular biology have shed light on the biological basis of Hodgkin’s lymphoma (HL). Knowledge of the biological basis has enabled us to understand that most Hodgkin and Reed-Sternberg (H-RS) cells are derived from germinal center B-cells and constitutive nuclear factor κB (NF-κ) activation is a common molecular feature. Molecular mechanisms responsible for constitutive NF-κB activation, Epstein Barr virus latent membrane protein 1, and defective IκBα and IκB kinase activation have been clarified in the past several years. A recent study revealed the biological link between 2 characteristic features of H-RS cells: CD30 overexpression and constitutive NF-κB activation. Ligand-independent signaling by over-expressed CD30 was shown to be a common mechanism that induced constitutive NF-κB activation in these cells. These results suggest the self-growth—promoting potential of H-RS cells and redefine the biology of HL composed of H-RS cells and lymphocytes.

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References

  1. Hodgkin T. On some morbid appearances of the absorbent glands and spleen.Med Chir Trans. 1832;17:68–114.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Kaufman D, Longo DL. Hodgkin’s disease.Crit Rev Oncol Hema- tol. 1992;13:135–156.

    Article  CAS  Google Scholar 

  3. Gruss HJ, Kadin ME. Pathophysiology of Hodgkin’s disease: functional and molecular aspects.Baillieres Clin Haematol. 1996;9: 417–446.

    Article  PubMed  CAS  Google Scholar 

  4. Hsu SM, Hsu PL. The nature of Reed-Sternberg cells: phenotype, genotype, and other properties.Crit Rev Oncog. 1994;5:213–245.

    Article  PubMed  CAS  Google Scholar 

  5. Kanzler H, Kuppers R, Hansmann ML, Rajewsky K. Hodgkin and Reed-Sternberg cells in Hodgkin’s disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells.J Exp Med. 1996;184:1495–1505.

    Article  PubMed  CAS  Google Scholar 

  6. Cossman J, Annunziata CM, Barash S, et al. Reed-Sternberg cell genome expression supports a B-cell lineage.Blood. 1999;94: 411–416.

    PubMed  CAS  Google Scholar 

  7. Kuppers R, Rajewsky K. The origin of Hodgkin and Reed/Stern- berg cells in Hodgkin’s disease.Annu Rev Immunol. 1998;16: 471–493.

    Article  PubMed  CAS  Google Scholar 

  8. Brauninger A, Hansmann ML, Strickler JG, et al. Identification of common germinal center-B-cell precursors in two patients with both Hodgkin’s disease and non-Hodgkin’s lymphoma.N Engl J Med. 1999;340:1239–1247.

    Article  PubMed  CAS  Google Scholar 

  9. Stein H, Hummel M. Cellular origin and clonality of classic Hodgkin’s lymphoma: immunophenotypic and molecular studies.Semin Hematol. 1999;36:233–241.

    PubMed  CAS  Google Scholar 

  10. Durkop H, Latza U, Hummel M, Eitelbach F, Seed B, Stein H. Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin’s disease.Cell. 1992;68:421–427.

    Article  PubMed  CAS  Google Scholar 

  11. Schwab U, Stein H, Gerdes J, et al. Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin’s disease and a subset of normal lymphoid cells.Nature. 1982;299:65–67.

    Article  PubMed  CAS  Google Scholar 

  12. Stein H, Gerdes J, Schwab U, et al. Identification of Hodgkin and Sternberg Reed cells as a unique cell type derived from a newly detected small-cell population.Int J Cancer. 1982;30:445–459.

    Article  PubMed  CAS  Google Scholar 

  13. Stein H, Mason DY, Gerdes J, et al. The expression of the Hodgkin’s disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells.Blood. 1985;66:848–858.

    CAS  PubMed  Google Scholar 

  14. Smith CA, Gruss HJ, Davis T, et al. CD30 antigen, a marker for Hodgkin’s lymphoma, is a receptor whose ligand defines an emerging family of cytokines with homology to TNF.Cell. 1993;73: 1349–1360.

    Article  PubMed  CAS  Google Scholar 

  15. Baker SJ, Reddy EP. Transducers of life and cell death: TNF receptor superfamily and associated proteins.Oncogene. 1996;12:1–9.

    PubMed  CAS  Google Scholar 

  16. Smith CA, Farrah T, Goodwin RG. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death.Cell. 1994;76:959–962.

    Article  PubMed  CAS  Google Scholar 

  17. Gruss HJ, Dower SK. Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas.Blood. 1995;85:3378–3404.

    CAS  PubMed  Google Scholar 

  18. Bargou RC, Leng C, Krappmann D, et al. High-level nuclear NF- kappa B and Oct-2 is a common feature of cultured Hodgkin/ Reed-Sternberg cells.Blood. 1996;87:4340–4347.

    PubMed  CAS  Google Scholar 

  19. Wood KM, Roff M, Hay RT. Defective IκBα in Hodgkin cell lines with constitutively active NFκB.Oncogene. 1998;16:2131–2139.

    Article  PubMed  CAS  Google Scholar 

  20. Cabannes E, Khan G, Aillet F, Jarrett RF, Hay RT. Mutations in the IκBα gene in Hodgkin’s disease suggest a tumour suppressor role for IκBα.Oncogene. 1999;18:3063–3070.

    Article  PubMed  CAS  Google Scholar 

  21. Emmerich F, Meiser M, Hummel M, et al. Overexpression of I kappa B alpha without inhibition of NF-kappa B activity and mutations in I kappa B alpha gene in Reed-Sternberg cells.Blood. 1999;94:3129–3134.

    PubMed  CAS  Google Scholar 

  22. Jungnickel B, Staratschek-Jox A, Brauninger A, et al. Clonal deleterious mutations in the IkBa gene in the malignant cells in Hodgkin’s lymphoma.J Exp Med. 2000;191:395–401.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Krappmann D, Emmerich F, Kordes U, Scharschmidt E, Dorken B, Scheidereit C. Molecular mechanisms of constitutive NF-κB/Rel activation in Hodgkin/Reed-Sternberg cells.Oncogene. 1999;18: 943–953.

    Article  PubMed  CAS  Google Scholar 

  24. Horie R, Watanabe T, Morishita Y, et al. Ligand-independent signaling by overexpressed CD30 drives NF-κB activation in Hodg- kin-Reed Sternberg cells.Oncogene. 2002;21:2493–2503.

    Article  PubMed  CAS  Google Scholar 

  25. Andreesen R, Osterholz J, Lohr GW, Bross KJ. A Hodgkin cell- specific antigen is expressed on a subset of auto- and alloactivated T (helper) lymphoblasts.Blood. 1984;63:1299–1302.

    PubMed  CAS  Google Scholar 

  26. Schwarting R, Gerdes J, Durkop H, Falini B, Pileri S, Stein H. BER- H2: a new anti-Ki-1 (CD30) monoclonal antibody directed at a for- mol-resistant epitope.Blood. 1989;74:1678–1689.

    PubMed  CAS  Google Scholar 

  27. Ellis TM, Simms PE, Slivnick DJ, Jäck HM, Fisher RI. CD30 is a signal-transducing molecule that defines a subset of human activated CD45RO+ T cells.J Immunol. 1993;151:2380–2389.

    PubMed  CAS  Google Scholar 

  28. Romagnani S, Del Prete G, Maggi E, Chilosi M, Caliqaris-Cappio F, Pizzolo G. CD30 and type 2 T helper (Th2) responses.J Leukoc Biol. 1995;57:726–730.

    Article  PubMed  CAS  Google Scholar 

  29. Del Prete G, De Carli M, Almerigogna F, et al. Preferential expression of CD30 by human CD4+ T cells producing Th2-type cytokines.FASEB J. 1995;9:81–86.

    Article  Google Scholar 

  30. Manetti R, Annunziato F, Biagiotti R, et al. CD30 expression by CD8+T cells producing type 2 helper cytokines: evidence for large numbers of CD8+CD30+ T cell clones in human immunodeficiency virus infection.J Exp Med. 1994;180:2407–2411.

    Article  PubMed  CAS  Google Scholar 

  31. Del Prete G, Maggi E, Pizzolo G, Romagnani S. CD30, Th2 cytokines and HIV infection: a complex and fascinating link.Immunol Today. 1995;16:76–80.

    Article  Google Scholar 

  32. Hamann D, Hilkens CM, Grogan JL, et al. CD30 expression does not discriminate between Th1- and Th2-type T cells.J Immunol. 1996;156:1387–1391.

    PubMed  CAS  Google Scholar 

  33. Alzona M, Jack HM, Fisher RI, Ellis TM. CD30 defines a subset of activated human T cells that produce IFN-γ and IL-5 and exhibit enhanced B cell helper activity.J Immunol. 1994;153:2861–2867.

    PubMed  CAS  Google Scholar 

  34. Abbondanzo SL, Sato N, Straus SE, Jaffe ES. Acute infectious mononucleosis. CD30 (Ki-1) antigen expression and histologic correlations.Am J Clin Pathol. 1990;93:698–702.

    Article  PubMed  CAS  Google Scholar 

  35. Biswas P, Smith CA, Goletti D, Hardy EC, Jackson RW, Fauci AS. Cross-linking of CD30 induces HIV expression in chronically infected T-cells.Immunity. 1995;2:587–596.

    Article  PubMed  CAS  Google Scholar 

  36. Ohtsuka E, Kikuchi H, Nasu M, Takita-Sonoda Y, Fujii H, Yokoyama S. Clinicopathological features of adult T-cell leukemia with CD30 antigen expression.Leuk Lymphoma. 1994;15:303–310.

    Article  PubMed  CAS  Google Scholar 

  37. Takeshita M, Akamatsu M, Ohshima K, et al. CD30 (Ki-1) expression in adult T-cell leukaemia/lymphoma is associated with distinctive immunohistological and clinical characteristics.Histopathol- ogy. 1995;26:539–546.

    Article  CAS  Google Scholar 

  38. Falini B, Pileri S, Pizzolo G, et al. CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy.Blood. 1995;85:1–14.

    PubMed  CAS  Google Scholar 

  39. Pallesen G The diagnostic significance of the CD30 (Ki-1) antigen.Histopathology. 1990;16:409–413.

    Article  PubMed  CAS  Google Scholar 

  40. Younes A, Consoli U, Zhao S, et al. CD30 ligand is expressed on resting normal and malignant human B lymphocytes.Br J Haema- tol. 1996;93:569–571.

    Article  CAS  Google Scholar 

  41. Pinto A, Aldinucci D, Gloghini A, et al. Human eosinophils express functional CD30 ligand and stimulate proliferation of a Hodgkin’s disease cell line.Blood. 1996;88:3299–3305.

    PubMed  CAS  Google Scholar 

  42. Gruss HJ, Pinto A, Gloghini A, et al. CD30 ligand expression in nonmalignant and Hodgkin’s disease-involved lymphoid tissues.Am J Pathol. 1996;149:469–448.

    PubMed  PubMed Central  CAS  Google Scholar 

  43. Gattei V, Degan M, Gloghini A, et al. CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin.Blood. 1997;89:2048–2059.

    CAS  PubMed  Google Scholar 

  44. Romagnani P, Annunziato F, Manetti R, et al. High CD30 ligand expression by epithelial cells and Hassal’s corpuscles in the medulla of human thymus.Blood. 1998;91:3323–3332.

    PubMed  CAS  Google Scholar 

  45. Josimovic-Alasevic O, Durkop H, Schwarting R, Backe E, Stein H, Diamantstein T. Ki-1 (CD30) antigen is released by Ki-1 positive tumor cells in vitro and in vivo, I: partial characterization of soluble Ki-1 antigen and detection of the antigen in cell culture super- natants and in serum by an enzyme-linked immunosorbent assay.EurJ Immunol. 1989;19:157–162.

    Article  CAS  Google Scholar 

  46. Hansen HP, Chiseler T, Kobarg J, Horn-Lohrens O, Havsteen B, Lemke H. A zinc metalloproteinase is responsible for the release of CD30 on human tumor cell lines.Int J Cancer. 1995;63:750–756.

    Article  PubMed  CAS  Google Scholar 

  47. Pizzolo G, Stein H, Josimovic-Alasevic O, et al. Increased serum levels of soluble IL-2 receptor, CD30 and CD8 molecules, and gamma-interferon in angioimmunoblastic lymphadenopathy: possible pathogenetic role of immunoactivation mechanisms.Br J Haematol. 1990;75:485–488.

    Article  PubMed  CAS  Google Scholar 

  48. Pfreundschuh M, Pohl C, Berenbeck C, et al. Detection of a soluble form of the CD30 antigen in sera of patients with lymphoma, adult T-cell leukemia and infectious mononucleosis.Int J Cancer. 1990;45:869–874.

    Article  PubMed  CAS  Google Scholar 

  49. Pizzolo G, Vinante F, Nadali G, et al. High serum level of soluble CD30 in acute primary HIV-1 infection.Clin Exp Immunol. 1997;108:251–253.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Dallenbach F, Josimovic-Alasevic O, Durkop H, et al. Soluble CD30 antigen in the sera of patients with adult T-cell lymphoma/ leukemia (ATL): a marker for disease activity. In: Knapp W, Dorken B, Gilks WR, et al, eds.Leukocyte Typing IV. Oxford, UK: Oxford University Press; 1989:426.

    Google Scholar 

  51. Nadali G, Tavecchia L, Zanolin E, et al. Serum level of the soluble form of the CD30 molecule identifies patients with Hodgkin’s disease at high risk of unfavorable outcome.Blood. 1998;91: 3011–3016.

    PubMed  CAS  Google Scholar 

  52. Zinzani PL, Pileri S, Bernardi M, et al. Clinical implications of serum levels of soluble CD30 in 70 adult anaplastic large-cell lymphoma patients.J Clin Oncol. 1998;16:1532–1537.

    Article  PubMed  CAS  Google Scholar 

  53. Luigi P, Pileri S, Bendandi M, et al. Clinical implications of serum levels of soluble CD30 in 70 adult anaplastic large-cell lymphoma patients.J Clin Oncol. 1998;16:1532–1537.

    Article  Google Scholar 

  54. Maggi E, Annunziato F, Manetti R, et al. Activation of HIV expression by CD30 triggering in CD4+ T cells from HIV-infected individuals.Immunity. 1995;3:251–255.

    Article  PubMed  CAS  Google Scholar 

  55. Lee CI, Park CG, Choi Y. T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors.J Exp Med. 1996;183:669–674.

    Article  PubMed  CAS  Google Scholar 

  56. Telford WG, Nam SY, Podack ER, Miller RA. CD30-regulated apoptosis in murine CD8 T cells after cessation of TCR signals.Cell Immunol. 1997;182:125–136.

    Article  PubMed  CAS  Google Scholar 

  57. Shanebeck KD, Maliszewski CR, Kennedy MK, et al. Regulation of murine B cell growth and differentiation by CD30 ligand.Eur J Immunol. 1995;25:2147–2153.

    Article  PubMed  CAS  Google Scholar 

  58. Bowen MA, Lee RK, Miragliotta G, Nam SY, Podack ER. Structure and expression of murine CD30 and its role in cytokine production.J Immunol. 1996;156:442–449.

    PubMed  CAS  Google Scholar 

  59. Kurts C, Carbone FR, Krummel MF, Koch KM, Miller JF, Heath WR. Signaling through CD30 protects against autoimmune diabetes mediated by CD8 T cells.Nature. 1999;398:341–344.

    Article  PubMed  CAS  Google Scholar 

  60. Cerutti A, Schaffer A, Shah S, et al. CD30 is a CD40-inducible molecule that negatively regulates CD40-mediated immunoglobulin class switching in non-antigen-selected human B cells.Immunity. 1998;9:247–256.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Amakawa R, Hakem A, Kundig TM, et al. Impaired negative selection of T cells in Hodgkin’s disease antigen CD30-deficient mice.Cell. 1996;84:551–562.

    Article  PubMed  CAS  Google Scholar 

  62. Gruss HJ, Ulrich D, Dower SK, Herrmann F, Brach MA. Activation of Hodgkin cells via the CD30 receptor induces autocrine secretion of interleukin 6 engaging the NF-κB transcription factor.Blood. 1996;87:2443–2449.

    PubMed  CAS  Google Scholar 

  63. Gruss HJ, Boiani N, Williams DE, Armitage RJ, Smith CA, Goodwin RG. Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines.Blood. 1994;83:2045–2056.

    CAS  PubMed  Google Scholar 

  64. Horie R, Watanabe T. CD30: expression and function in health and disease.Semin Immunol. 1998;10:457–470.

    Article  PubMed  CAS  Google Scholar 

  65. Ghosh S, May MJ, Kopp EB. NF-kappaB and Rel proteins: evolu- tionarily conserved mediators of immune responses.Annu Rev Immunol. 1998;16:225–260.

    Article  PubMed  CAS  Google Scholar 

  66. Karin M. How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex.Oncogene. 1999;18:6867–6874.

    Article  PubMed  CAS  Google Scholar 

  67. Miyamoto S, Verma IM. Rel/NF-kappaB/I kappaB story.Adv Cancer Res. 1995;66:255–292.

    Article  PubMed  CAS  Google Scholar 

  68. Siebenlist U, Franzoso G, Brown K. Structure, regulation and function of NF-κB.Ann Rev Cell Biol. 1994;10:405–455.

    Article  PubMed  CAS  Google Scholar 

  69. Chen FE, Ghosh G. Regulation of DNA binding by Rel/NF- kappaB transcription factors: structural views.Oncogene. 1999;18:6845–6852.

    Article  PubMed  CAS  Google Scholar 

  70. Baeuerle PA, Baichwal VR. NF-kappaB as a frequent target for immunosuppressive and anti-inflammatory molecules.Adv Immunol. 1997;65:111–137.

    Article  PubMed  CAS  Google Scholar 

  71. Barnes PJ, Karin M. Nuclear factor-κB-a pivotal transcription factor in chronic inflammatory diseases.N Engl J Med. 1997;336: 1066–1071.

    Article  PubMed  CAS  Google Scholar 

  72. Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors.Oncogene. 1999;18:6853–6866.

    Article  PubMed  CAS  Google Scholar 

  73. Kaltschmidt B, Uherek M, Wellmann H, Volk B, Kaltschmidt C. Inhibition of NF-kappaB potentiates amyloid beta-mediated neuronal apoptosis.ProcNatl Acad Sci USA. 1999;96:9409–9414.

    Article  CAS  Google Scholar 

  74. Korner M,Tarantino N, Debre P. Constitutive activation of NF-κB in human thymocytes.Biochem Biophys Res Commun. 1991;181: 80–86.

    Article  PubMed  CAS  Google Scholar 

  75. Krishnamoorthy RR, Crawford MJ, Chaturvedi MM, et al. Photo- oxidative stress down-modulates the activity of nuclear factor- kappaB via involvement of caspase-1, leading to apoptosis of pho- toreceptor cells.J Biol Chem. 1999;274:3734–3743.

    Article  PubMed  CAS  Google Scholar 

  76. Hinz M, Loser P, Mathas S, Krappmann D, Dorken B, Scheidereit C. Constitutive NF-kappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of anti- apoptotic genes in Hodgkin/Reed-Sternberg cells.Blood. 2001;97: 2798–2807.

    Article  PubMed  CAS  Google Scholar 

  77. Rayet B, Gelinas C. Aberrant rel/nfκb genes and activity in human cancer.Oncogene. 1999;18:6938–6947.

    Article  PubMed  CAS  Google Scholar 

  78. Staratschek-Jox A, Kotkowski S, Belge G, et al. Detection of Epstein-Barr virus in Hodgkin-Reed-Sternberg cells: no evidence for the persistence of integrated viral fragments in latent membrane protein-1 (LMP-1)-negative classical Hodgkin’s disease.Am J Pathol. 2000;156:209–216.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Gires O, Zimber-Strobl U, Gonnella R, et al. Latent membrane protein 1 of Epstein-Barr virus mimics a constitutively active receptor molecule.EMBO J. 1997;16:6131–6140.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Izumi KM, Kieff ED. The Epstein -Barr virus oncogene product latent membrane protein 1 engages the tumor necrosis factor receptor-associated death domain protein to mediate B lymphocyte growth transformation and activate NF-κB.Proc Natl Acad Sci USA. 1997;94:12592–12597.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Izumi KM, Kaye KM, Kieff ED. The Epstein-Barr virus LMP-1 amino acid sequence that engages tumor necrosis factor receptor associated factors is critical for primary B lymphocyte growth transformation.Proc Natl Acad Sci USA. 1997;94:1447–1452.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. McFarland EDC, Izumi KM, Mosialos G. Epstein-Barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF-κB.Oncogene. 1999;18:6959–6954.

    Article  CAS  Google Scholar 

  83. Teramoto N, Cao L, Kawasaki N, et al. Variable expression of Epstein-Barr virus latent membrane protein 1 in Reed-Sternberg cells of Hodgkin’s disease.Acta Med Okayama. 1996;50:267–270.

    PubMed  CAS  Google Scholar 

  84. Fiumara P, Snell V, Li Y, Mukhopadhyay A, et al. Functional expression of receptor activator of nuclear factor kappaB in Hodgkin disease cell lines.Blood. 2001;98:2784–2790.

    Article  PubMed  CAS  Google Scholar 

  85. Horie R, Aizawa S, Nagai M, et al. A novel domain in the CD30 cytoplasmic tail mediates NF-κB activation.Int Immunol. 1998;10: 203–210.

    Article  PubMed  CAS  Google Scholar 

  86. Maniatis T. Catalysis by a multiprotein IκB kinase complex.Science. 1997;278:818–819.

    Article  PubMed  CAS  Google Scholar 

  87. Gedrich RW,Gilfillan MC,Duckett CS, Van Dongen JL, Thompson CB. CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins.J Biol Chem. 1996;271: 12852–12858.

    Article  PubMed  CAS  Google Scholar 

  88. Lee SY, Lee SY, Kandala G, Liou ML, Liou HC, Choi Y CD30/ TNF receptor-associated factor interaction: NF-kappaB activation and binding specificity.Proc Natl Acad Sci USA. 1996;93: 9699–9703.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  90. Boucher LM, Marengere LE, Lu Y, Thukral S, Mak TW. Binding sites of cytoplasmic effectors TRAF1,2, and 3 on CD30 and other members of the TNF receptor superfamily.Biochem Biophys Res Commun. 1997;233:592–600.

    Article  PubMed  CAS  Google Scholar 

  91. Duckett CS, Gedrich RW, Gilfillan MC, Thompson CB. Induction of nuclear factor κB by the CD30 receptor is mediated by TRAF1 and TRAF2.Mol Cell Biol. 1997;17:1535–1542.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Hu HM, O’Rourke K, Boguski MS, Dixit VM. A novel RING finger protein interacts with the cytoplasmic domain of CD40.J Biol Chem. 1994;269:30069–30072.

    PubMed  CAS  Google Scholar 

  93. Rothe M, Wong SC, Henzel WJ, Goeddel DV. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor.Cell. 1994;78:681–692.

    Article  PubMed  CAS  Google Scholar 

  94. Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S, Baltimore D. Involvement of CRAF1, a relative of TRAF, in CD40 signaling.Science. 1995;267:1494–1498.

    Article  PubMed  CAS  Google Scholar 

  95. Mosialos G, Birkenbach M,Yalamanchili R,VanArsdale T, Ware C, Kieff E. The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family.Cell. 1995;80:389–399.

    Article  PubMed  CAS  Google Scholar 

  96. Regnier CH, Tomasetto C, Moog-Lutz C, et al. Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma.J Biol Chem. 1995;270:25715–25721.

    Article  PubMed  CAS  Google Scholar 

  97. Sato T, Irie S, Reed JC. A novel member of the TRAF family of putative signal transducing proteins binds to the cytoplasmic domain of CD40.FEBS Lett. 1995;358:113–118.

    Article  PubMed  CAS  Google Scholar 

  98. Song HY, Donner DB. Association of a RING finger protein with the cytoplasmic domain of the human type-2 tumor necrosis factor.Biochem J. 1995;309:825–829.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  100. Ishida TK, Tojo T, Aoki T, et al. TRAF-5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling.Proc Natl Acad Sci USA. 1996;93:9437–9442.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV. TRAF6 is a signal transducer for interleukin-1.Nature. 1996;383:443–446.

    Article  PubMed  CAS  Google Scholar 

  102. Ishida T, Mizushima S, Azuma S, et al. Identification of TRAF6, a novel TRAF protein that mediates signaling from an amino-termi- nal domain of the CD40 cytoplasmic region.J Biol Chem. 1996;271: 28745–28748.

    Article  PubMed  CAS  Google Scholar 

  103. Rothe M, Sarma V, Dixit VM, Goeddel DV. TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40.Science. 1995;269:1424–1427.

    Article  PubMed  CAS  Google Scholar 

  104. 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: 19935–19942.

    Article  PubMed  CAS  Google Scholar 

  105. Duckett CS, Thompson CB. CD30-dependent degradation of TRAF2: implications for negative regulation of TRAF signaling and the control of cell survival.Genes Dev. 1997;11:2810–2821.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Grell M, Zimmermann G, Gottfried E, et al. Induction of cell death by tumor necrosis factor (TNF) receptor 2, CD40 and CD30: a role for TNF-R1 activation by endogenous membrane-anchored TNF.EMBO J. 1999;18:3034–3043.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Chan FK, Chun HJ, Zheng L, Siegel RM, Bui KL, Lenardo MJ. A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling.Science. 2000;288:2351–2354.

    Article  PubMed  CAS  Google Scholar 

  108. Papoff G, Hausler P, Eramo A, et al. Identification and characterization of a ligand-independent oligomerization domain in the extracellular region of the CD95 death receptor.J Biol Chem. 1999;274:38241–38250.

    Article  PubMed  CAS  Google Scholar 

  109. Siegel RM, Frederiksen JK, Zacharias DA, et al. Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations.Science. 2000;288:2354–2357.

    Article  PubMed  CAS  Google Scholar 

  110. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM. An antagonist decoy receptor and a death domain-containing receptor for TRAIL.Science. 1997;277:815–818.

    Article  PubMed  CAS  Google Scholar 

  111. Sheridan JP, Marsters SA, Pitti RM, et al. Control of TRAIL- induced apoptosis by a family of signaling and decoy receptors.Science. 1997;277:818–821.

    Article  PubMed  CAS  Google Scholar 

  112. Izban KF, Ergin M, Martinez RL, Alkan S. Expression of the tumor necrosis factor receptor-associated factors (TRAFs) 1 and 2 is a characteristic feature of Hodgkin and Reed-Sternberg cells.Mod Pathol. 2000;13:1324–1331.

    Article  PubMed  CAS  Google Scholar 

  113. Durkop H, Foss HD, Demel G, Klotzbach H, Hahn C, Stein H. Tumor necrosis factor receptor-associated factor 1 is overexpressed in Reed-Sternberg cells of Hodgkin’s disease and Epstein-Barr virus-transformed lymphoid cells.Blood. 1999;93:617–623.

    PubMed  CAS  Google Scholar 

  114. Arch RH, Gedrich RW, Thompson CB. Translocation of TRAF proteins regulates apoptotic threshold of cells.Biochem Biophys Res Commun. 2000;272:936–945.

    Article  PubMed  CAS  Google Scholar 

  115. Zapata JM, Krajewska M, Krajewski S, et al. TNFR-associated factor family protein expression in normal tissues and lymphoid malignancies.J Immunol. 2000;165:5084–5096.

    Article  PubMed  CAS  Google Scholar 

  116. Horie R, Watanabe T, Watanabe M, et al. Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in the Hodgkin-Reed-Sternberg cells.Am J Pathol. 2002;160:1647–1654.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Bargou RC, Emmerich F, Krappmann D, et al. Constitutive nuclear factor-kB-RelA activation is required for proliferation and survival of Hodgkin’s disease tumor cells.J Clin Invest. 1997;100: 2961–2969.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Kapp U, Yeh WC, Patterson B, et al. Interleukin 13 is secreted by and stimulates the growth of Hodgkin and Reed-Sternberg cells.J Exp Med. 1999;189:1939–1946.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Croager EJ, Muir TM, Abraham LJ. Analysis of human and mouse promoter region of the non-Hodgkin’s lymphoma-associated CD30 gene.J Interferon Cytokine Res. 1998;18:915–920.

    Article  PubMed  CAS  Google Scholar 

  120. Durkop H, Oberbarnscheidt M, Latza U, et al. The restricted expression pattern of the Hodgkin’s lymphoma-associated cytokine receptor CD30 is regulated by a minimal promoter.J Pathol. 2000;192:182–193.

    Article  PubMed  CAS  Google Scholar 

  121. Durkop H, Oberbarnscheidt M, Latza U, et al. Structure of the Hodgkin’s lymphoma-associated human CD30 gene and the influence of a microsatellite region on its expression in CD30 (+) cell lines.Biochim Biophys Acta. 2001;1519:185–191.

    Article  PubMed  CAS  Google Scholar 

  122. Croager EJ, Gout AM, Abraham LJ. Involvement of Sp1 and microsatellite repressor sequences in the transcriptional control of the human CD30 gene.Am J Pathol. 2000;156:1723–1731.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Kadin ME. Regulation of CD30 antigen expression and its potential significance for human disease.Am J Pathol. 2000;156: 1479–1984.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Fourth Department of Internal Medicine, Kitasato University, School of Medicine, 1-15-1 Sagamihara, 228-8555, Kanagawa, Japan

    Ryouichi Horie & Masaaki Higashihara

  2. Division of Pathology, Department of Cancer Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Ryouichi Horie & Toshiki Watanabe

Authors
  1. Ryouichi Horie
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  2. Masaaki Higashihara
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  3. Toshiki Watanabe
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Correspondence to Ryouichi Horie.

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Horie, R., Higashihara, M. & Watanabe, T. Hodgkin’s Lymphoma and CD30 Signal Transduction. Int J Hematol 77, 37–47 (2003). https://doi.org/10.1007/BF02982601

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  • DOI: https://doi.org/10.1007/BF02982601

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