Fas Splicing Variants and their Effect on Apoptosis

  • Giovina Ruberti
  • Isabella Cascino
  • Giuliana Papoff
  • Adriana Eramo
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 406)

Abstract

Higher vertebrates frequently contain multigene families of related ligands and their receptors, often with overlapping specificities. Presumably such an organization allows for greater flexibility in the timing and tissue distribution of these molecules. A further level of complexity is introduced by the fact that variants of the same growth factor or receptor can be encoded as alternative transcripts of the same gene. Such variants may remain membrane associated or may be efficiently secreted.

Keywords

Death Domain Acidic Sphingomyelinase Resistant Cell Clone HUT78 Cell Line Peripheral Blood Mononuclear Cell Activation 
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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References

  1. 1.
    C.W.J. Smith, J. G. Patton, and B. Nadal-Ginard, Alternative splicing in the control of gene expression, Annu. Rev. Genet. 23: 527 (1989).PubMedCrossRefGoogle Scholar
  2. 2.
    P.M. Bingham, T. -B. Chou, I. Mims, and Z. Zachar, On/Off regulation of gene expression at the level of splicing, Trends Genet. 4: 134 (1988).PubMedCrossRefGoogle Scholar
  3. 3.
    L.R. Bell, E.M. Maine, R. Schedl, and T.W. Cline, Sex-lethal, a drosophila sex determination switch gene, inhibits sex-specific RNA splicing and sequence similarity to RNAbinding proteins, Cell 55:1037 (1988).Google Scholar
  4. 4.
    R.T. Boggs, R. Gregor, S. Idriss, J.M. Belote, and M. Mc Keown, Regulation of sexual differentiation in D. melanogaster via alternative splicing of RNA frome the transformer gene, Cell 50: 739 (1987).PubMedCrossRefGoogle Scholar
  5. 5.
    C.A. Smith, T. Farrah, and R.G. Goodwin, The TNF receptor superfamily of cellular and viral proteins: activation, costimulation and death, Cell 76: 959 (1994).PubMedCrossRefGoogle Scholar
  6. 6.
    S. Nagata, and P. Golstein, The Fas death factor, Science 267: 1449 (1995).PubMedCrossRefGoogle Scholar
  7. 7.
    P. Vandenabeele, W. Declercq, R. Beyaert, and W. Fiers, Two tumour necrosis factor receptors: structure and function, TIBS 5: 392 (1995).Google Scholar
  8. 8.
    M.G. Cifone, R. De Maria, P. Roncaioli, M.R. Rippo, M. Azuma, L.L. Lanier, A. Santoni, R. and Testi, R, Apoptotic signaling through CD95 (Fas/Apo-1) activates and acidic sphingomyelinase, J. Exp. Med. 180: 1547 (1994).PubMedCrossRefGoogle Scholar
  9. 9.
    B.M. Gill, H. Nishikata, G. Chan, T.L. Delovitch, and A. Ochi, Fas antigen and shingomyelin-ceramide turnover-mediated signaling: role in life and death of T lymphocytes, Immunol. Rev. 142: 113 (1995)CrossRefGoogle Scholar
  10. 10.
    E. Gulbins, R. Bissonette, A. Mahboubi, S. Martin, W. Nishioka, T. Brunner, G. Baier, G. Baier-Bitterlich, C. Byrd, F. Lang, R. Kolesnick, A. Altman, and D. Green, Fas-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway, Immunity 2: 341 (1995).PubMedCrossRefGoogle Scholar
  11. 11.
    C. Tepper, S. Jayadev, B. Liu, A. Bielawska, R. Wolff, S. Yonehara, Y.A. Hannun, and M.F. Seldin, Role of ceramide as an endogenous mediator of Fas-induced cytotoxicity, Proc. Natl. Acad. Sci. USA 92: 8443 (1995).PubMedCrossRefGoogle Scholar
  12. 12.
    M.G. Cifone, R. Roncaioli, R. De Maria, G. Camarda, A. Santoni, G. Ruberti, and R. Testi, Multiple pathways originate at the Fas/Apo-1 (CD95) receptor: sequential involvement of phosphatidylcholinespecific phospholipase C and acidic sphingomyelinase in the propagation of the apoptotic signal, EMBO J. 14: 5859 (1995).PubMedGoogle Scholar
  13. 13.
    M.R. Alderson, R.J. Armitage, E. Maraskowsky, T.W. Tough, E. Roux, K. Schooley, F. Ramsdell, and D.H. Lynch, Fas transduces activation signals in normal human T lymphocytes, J. Exp. Med. 178: 2231 (1993).PubMedCrossRefGoogle Scholar
  14. 14.
    R.A. Heller, and M. Kronke,Tumor necrosis factor-mediated signaling pathways, J. Cell Biol. 126: 5 (1994).PubMedCrossRefGoogle Scholar
  15. 15.
    J. Cheng, T. Zhou, C. Liu, J.P. Shapiro, M.J. Brauer, M.C. Kiefer, P.J. Barr, and J.D. Mountz, Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule, Science 263: 1759 (1994).PubMedCrossRefGoogle Scholar
  16. 16.
    I. Cascino, G. Fiucci, G. Papoff, and G. Ruberti, Three functional soluble forms of the human apoptosisinducing Fas molecule are produced by alternative splicing, J. Immunol. 154: 2706 (1995).PubMedGoogle Scholar
  17. 17.
    G. Papoff, I. Cascino, A. Eramo, G. Starace, D.H. Lynch, and G. Ruberti, An N-terminal domain shared by Fas/Apo-1 (CD95) soluble variants prevents cell death in vitro, (submitted).Google Scholar
  18. 18.
    C. Liu, J. Cheng, and J.D. Mountz, Differential expression of human Fas mRNA species upon peripheral blood mononuclear cell activation, Biochem. J. 310: 957 (1995)PubMedGoogle Scholar
  19. 19.
    I. Behrmann, H. Walczak, and P.H. Krammer, Structure of the human APO-1 gene, Eur. J. Immunol. 24: 3057 (1994).PubMedCrossRefGoogle Scholar
  20. 20.
    J. Cheng, L. Changdan, W.J. Koopman, and J.D. Mountz, Characterization of the human Fas gene. Exon/Intron organization and promoter region, J. Immunol. 154: 1239 (1995).PubMedGoogle Scholar
  21. 21.
    F. Rieux-Laucat, F. Le Deist, C. Hivroz, I.A.G. Roberts, K.M. Debatin, A. Fischer, and J.P. de Villartay, Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity, Science 268: 1347 (1995).PubMedCrossRefGoogle Scholar
  22. 22.
    G.H. Fisher, F.J. Rosenberg, S.E. Straus, J.K. Dale, L.A. Middelton, A.Y. Lin, W. Strober, M.J. Lenardo, J.M. and Puck, Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome, Cell 81: 935 (1995).PubMedCrossRefGoogle Scholar
  23. 23.
    N. Itoh, and S. Nagata, A novel protein domain required for apoptosis, J. Biol. Chem. 268: 10932 (1993).PubMedGoogle Scholar
  24. 24.
    L.A. Tartaglia, T.M. Ayres, G.H.W. Wong, and D.V. Goeddel, A novel domain within the 55 Kd TNF receptor signals cell death, Cell 74: 845 (1993).PubMedCrossRefGoogle Scholar
  25. 25.
    N. Itoh, S. Yonehara, A. Ishii, M. Yonehara, S. Mizushima,M. Sameshima, A. Hase, Y. Seto, and S. Nagata, The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis, Cell 66: 233 (1991).PubMedCrossRefGoogle Scholar
  26. 26.
    M.R. Alderson, T.W. Tough, S. Braddy, T. Davis-Smith, E. Roux, K. Schooley, R.E. Miller, and D.H. Lynch, Regulation of apoptosis and T cell activation by Fas-specific monoclonal antibodies. Int. Immunol. 6: 1799 (1994).PubMedCrossRefGoogle Scholar
  27. 27.
    P.H. Krammer, et al., The role of APO-1 mediated apoptosis in the immune system, Immunol. Rev. 142: 175 (1994).PubMedCrossRefGoogle Scholar
  28. 28.
    L.B. Owen-Schaub, S. Yonehara, W.L. Crump, and E.A. Grimm, DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement,Cellular Immunol. 140: 197 (1992).Google Scholar
  29. 29.
    C. Klas, K.-M. Debatin, R.R. Jonker, and P.H. Krammer, Activation interferes with the APO-1 patway in mature human T cells, Int. Immunol. 5: 625 (1993).PubMedCrossRefGoogle Scholar
  30. 30.
    A. Anel, M. Buferne, C. Boyer, A.-M. Schmitt-Verhulst, and P. Golstein, T cell receptor-induced Fas ligand expression in cytotoxic T lymphocyte clones is blocked by protein tyrosine kinase inhibitors and Cyclosporin A, Eur. J. Immunol. 24: 2469 (1994).PubMedCrossRefGoogle Scholar
  31. 31.
    F. Vignaux, E. Vivier, B. Malissen,V. Depraetere, S. Nagata, and P. Golstein, TCR/CD3 coupling to Fas-based cytotoxicity, J. Exp. Med. 181: 781 (1995).PubMedCrossRefGoogle Scholar
  32. 32.
    J. Dhein, H. Walczak, C. Baumier, K.-M. Debatin, and P.H. Krammer, Autocrine T-cell suicide mediated by APO-1/(Fas/CD95), Nature 373: 438 (1995).PubMedCrossRefGoogle Scholar
  33. 33.
    T. Brunner, R.J. Mogil, D. La Face, N.J. Yoo, A. Mahboubi, F. Echeverri, S.J. Martin, W.R. Force, D.H. Lynch, C.F. Ware, and D.R.Green, Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T cell hybridomas, Nature 373: 441 (1995).Google Scholar
  34. 34.
    S.-T. Ju, D.J. Panka, H. Cui, R.M. Ettinger, D.H. El-Khatib, B. Sherr, Z. Stanger, and A. Marshak-Rothstein, Fas (CD95)/FasL interactions required for programmed cell death after T-cell activation, Nature 373: 444 (1995).PubMedCrossRefGoogle Scholar
  35. 35.
    M.R. Alderson, T.W. Tough, T. Davis-Smith, S. Braddy, B. Falk, K.A. Schooley, R.G. Goodwin, C.A. Smith, F. Ramsdell, and D.H. Lynch, Fas ligand mediates activation-induced cell death in human T lymphocytes, J. Exp. Med. 181: 71 (1995).PubMedCrossRefGoogle Scholar
  36. 36.
    F. Leithauser, J. Dhein, G. Mechtersheimer, K. Koretz, S. Brunderlein, C. Henne, A. Schmidt, K.-M. Debatin, P.H. Krammer, and P. Moller, Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells, Lab. Invest. 69: 415 (1993).PubMedGoogle Scholar
  37. 37.
    L.B. Owen-Schaub, R. Radinsky, E. Kruzel, K. Berry, and S. Yonehara, Anti-Fas mediated apoptosis in nonhematopoietic tumors: neither Fas/Apo-I nor bcl-2 expression is predictive of biological responsiveness, Cancer Res 54: 1580 (1994).PubMedGoogle Scholar
  38. 38.
    M.Y. Mapara, R. Bargou, C. Zugck, H. Dohner, F. Ustaoglu, R.R. Jonker, P.H. Krammer, and B. Dorken, APO-1 mediated apoptosis or proliferation in human chronic B lymphocytic leukemia: correlation with bcl-2 oncogene expression, Eur. J. Immunol. 23: 702 (1993).PubMedCrossRefGoogle Scholar
  39. 39.
    K.-M. Debatin, C.K. Goldman, T.A. Waldmann and P.H. Krammer, APO-1 induced apoptosis of leukemia cells from patients with adult T-cell leukemia, Blood 81: 2972 (1993).PubMedGoogle Scholar
  40. 40.
    G. Natoli, A. Ianni, A. Costanzo, G. De Petrillo, I. Ilari, P. Chirillo, C. Balsano, and M. Levrero, Resistance to Fas-mediated apoptosis in human hepatoma cells, Oncogene 11:1157 (1995).Google Scholar
  41. 41.
    L.B. Owen-Schaub, L.S. Angelo, R. Radinsky, C.F. Ware, T.G. Gesner, and D.P. Bartos, Soluble Fas/Apo-1 in tumor cells: a potential regulator of apoptosis, Cancer Letters 94: 1 (1995).PubMedCrossRefGoogle Scholar
  42. 42.
    D.P.M. Hughes, and I.N. Crispe, A Naturally occurring soluble isoforms of murine Fas generated by alternative splicing, J. Exp. Med. 182: 1395 (1995).PubMedCrossRefGoogle Scholar
  43. 43.
    E. Knipping, K.-M. Debatin, K. Stricker, B. Heilig, A. Eder, and P.H. Krammer, Identification of soluble APO-1 in supernatants of human B- and T-cell lines and increased serum levels in B- and T-cell leukemias, Blood 85: 1562 (1995).PubMedGoogle Scholar
  44. 44.
    N. Goel, D.T. Ulrich, E. St Clair, J.A. Fleming, D.H. Lynch, M.F. Seldin, Lack of correlation of serum soluble Fas levels and autoimmune disease, Arthritis Rheum. 38: 1738 (1995).PubMedCrossRefGoogle Scholar
  45. 45.
    R.A. Smith, and C. Baglioni, The active form of tumor necrosis factor is a trimer, J. Biol. Chem. 262:6951 (1 987).Google Scholar
  46. 46.
    M.J. Eck, and S.R. Sprang, The structure of tumor necrosis factor at 2.6 A resolution, J. Biol. Chem. 264: 17595 (1989).PubMedGoogle Scholar
  47. 47.
    E.Y. Jones, D.I. Stuart, and N.P.C. Walker, Structure of tumor necrosis factor, Nature 338: 225 (1989).PubMedCrossRefGoogle Scholar
  48. 48.
    M.J. Eck, M. Ultsch, E. Rinderknecht, A.M. deVos, and S.R. Spring, The structure of human lymphotoxin (tumor necrosis factor beta) at 1.9- A resolution, J. Biol. Chem. 267: 2119 (1992).PubMedGoogle Scholar
  49. 49.
    D. Banner, A. D’Arcy, W. Janes, R. Gentz, H.-J. Schoenfeld, C. Broger, H. Loetscher, and W. Lesslauer, Crystal structure of the soluble human 55kd TNF receptor-human TNF(3 complex: implications for TNF receptor activation, Cell 73: 431 (1993).PubMedCrossRefGoogle Scholar
  50. 50.
    S. Yonehara, A. Ishii, and M. Yonehara, A cell killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of TNF, J. Exp. Med. 169: 1747 (1989).PubMedCrossRefGoogle Scholar
  51. 51.
    M. Tanaka, T. Suda, T. Takahashi, and S. Nagata, Expression of the functional soluble form of human Fas ligand in activated lymphocytes, EMBO J. 14: 1129 (1995).PubMedGoogle Scholar
  52. 52.
    A. Basu, M. Raghmath, S. Bishayee, and M. Das, Inhibition of tyrosine kinase activity of the epidermal growth factor (EGF) receptor by a truncated receptor form that binds to EGF: role for interreceptor interaction in kinase regulation, Mol. Cell. Biol. 9: 671 (1989).PubMedGoogle Scholar
  53. 53.
    L.M. Obeid, C.M. Linardic, L.A. Karolak, and Y.A. Hannun, Programmed cell death induced by ceramide, Science 259: 1769 (1993).PubMedCrossRefGoogle Scholar
  54. 54.
    I. Cascino, G. Papoff, R. De Maria, R. Testi, and G. Ruberti, Fas/Apo- 1/CD95 receptor lacking the intracytoplasmic signaling domain protects tumor cells from Fas-mediated apoptosis, J. Immunol. 156: 13 (1996).PubMedGoogle Scholar
  55. 55.
    S. Nagata, and T. Suda, Fas and Fas ligand: 1pr and gld mutations, Immunol. Today 16: 39 (1995).PubMedCrossRefGoogle Scholar
  56. 56.
    A.M. Chinnaiyan, K. O’Rourke, M. Tewari, and V.M. Dixit, FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis, Cell 81: 505 (1995).PubMedCrossRefGoogle Scholar
  57. 57.
    M.P. Boldin, E.E. Varfolomeev, Z. Pancer, I.L. Mett, J.H. Camonis, and D. Wallach, A novel protein that interact with the death domain of Fas/Apo-1 contains a sequence motif related to the death domain, J. Biol. Chem. 270: 7795 (1995).PubMedCrossRefGoogle Scholar
  58. 58.
    H. Hsu, J. Xiong, and D.V. Goeddel, The TNF receptor 1-associated protein TRADD signals cell death and NF-kB activation, Cell 81: 495 (1995).PubMedCrossRefGoogle Scholar
  59. 59.
    B.Z. Stanger, P. Leder, T.-H. Lee, E. Kim, and B. Seed, RIP: a novel protein containing a death domain that interacts with Fas/Apo-1 (CD95) in Yeast and causes cell death, Cell 81: 513 (1995).PubMedCrossRefGoogle Scholar
  60. 60.
    K. White, M.E. Grether, J.M. Abrams, L. Young, K. Farrell, and H. Steller, Genetic control of programmed cell death in Drosophila, Science 264: 677 (1994).PubMedCrossRefGoogle Scholar
  61. 61.
    P. Golstein, D. Marguet, and V. Depraetere, Homology between Reaper and the cell death domains of Fas and TNFR1, Cell 81: 185 (1995).PubMedCrossRefGoogle Scholar
  62. 62.
    E. Feinstein, A. Kimchi, D. Wallach, M. Boldin, and E. Varfolomeev, The death domain: a module shared by proteins with diverse cellular functions, TIBS 20: 342 (1995).PubMedGoogle Scholar
  63. 63.
    K. Hofman, and J. Tschopp, The death domain motif in Fas (Apo-1) and TNF receptor is present in proteins involved in apoptosis and axonal guidance, FEBS Lett. 371: 321 (1995).CrossRefGoogle Scholar
  64. 64.
    F.C. Kischkel, S. Hellbardt, I. Behrmann, M. Germer, M. Pawlita, P.H. ‘Crammer, and M.E. Peter, Cytotoxicity-dependent APO-1 (Fas/CD95)- associated proteins form a death-inducing signaling complex (DISC) with the receptor, EMBO J. 14: 5579 (1995).PubMedGoogle Scholar
  65. 65.
    X. Su, T. Zhou, Z. Wang, P. Yang, R.S. Jope, J.D. Mountz, Defective expression of hematopoietic cell protein tyrosine phosphatase (HCP) in lymphoid cells blocks Fas-mediated apoptosis, Immunity 2: 353 (1995).PubMedCrossRefGoogle Scholar
  66. 66.
    T. Sato, S. Irie, S. Kitada, and J.C. Reed, FAP-1: a protein tyrosine phosphatase that associates with Fas, Science 268: 411 (1995).PubMedCrossRefGoogle Scholar
  67. 67.
    R.C. Bargou, P.T. Daniel, M.Y. Mapara, K. Bommert, C. Wagener, B. Kallinich, H.D. Royer, and B. Dorken, Expression of the bcl-2 gene family in normal and malignant breast tissue: low bax-a expression in tumor cells correlates with resistance towards apoptosis, Int. J. Cancer 60: 854 (1995).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Giovina Ruberti
    • 1
  • Isabella Cascino
    • 1
  • Giuliana Papoff
    • 1
  • Adriana Eramo
    • 1
  1. 1.Department of Immunobiology Institute of Cell BiologyNational Research CouncilRomeItaly

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