Perforin-dependent nuclear targeting of granzymes: A central role in the nuclear events of granule-exocytosis-mediated apoptosis?

Immunology and Cell Biology

Volumn 77, Issue 3, 1999, Pages 206-215

  Blink, Elizabeth J ^a   Trapani, Joseph A ^b   Jans, David A ^a  

^a AUSTRALIAN NATIONAL UNIVERSITY   (Australia)

^b AUSTIN RESEARCH INSTITUTE   (Australia)

Author keywords

Cytolytic granule mediated apoptosis; DNA fragmentation; Granzyme; Nuclear protein import; Perforin

Indexed keywords

GRANZYME A; GRANZYME B; NUCLEAR PROTEIN; PERFORIN;

APOPTOSIS; CAENORHABDITIS ELEGANS; CELL NUCLEUS; CELL NUCLEUS MEMBRANE; CONFERENCE PAPER; EXOCYTOSIS; NONHUMAN; PROTEIN LOCALIZATION; TARGET CELL;

ANIMALS; APOPTOSIS; CASPASES; CELL NUCLEUS; ENZYME ACTIVATION; EXOCYTOSIS; GRANZYMES; HUMANS; MEMBRANE GLYCOPROTEINS; MICE; MICE, KNOCKOUT; MICROSCOPY, CONFOCAL; PORE FORMING CYTOTOXIC PROTEINS; RATS; SERINE ENDOPEPTIDASES; SIGNAL TRANSDUCTION;

EID: 0032974963     PISSN: 08189641     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1440-1711.1999.00817.x     Document Type: Conference Paper

References (101)

1. 1 Darmon AJ, Nicholson DW, Bleackley RC. Activation of the apoptotic proteasc CPP32 by cytotoxic T-cell-derived granzyme B. Nature 1993; 377: 446-8.
2. 2 Prescott LM, Harley JP, Klein DA. Microbiology, 3rd edn. Boston: Wm C Brown Publishers, 1996.
3. 3 Moretta A. Molecular mechanism in cell-mediated cytotoxicity. Cell 1997; 90: 13-18.
4. 4 Janeway CA, Travers P. Immuno Biology: The immune system in health and disease, 2nd edn. London: Current Biology Limited, 1996.
5. 5 Lazebnik YA, Cole S, Cooke CA, Nelson WG, Earnshaw WC. Nuclear events of apoptosis in vitro in cell-free mitotic extracts: A model system for analysis of the active phase of apoptosis. J. Cell Biol. 1993; 123: 7-22.
6. 6 Patel T, Gores GJ, Kaufmann SH. The role of proteases during apoptosis. FASEB J. 1996; 10: 587-97.
7. 7 Thornberry NA, Rano TA, Peterson EP et al. A combinatorial approach defines specificities of members of the caspase family and granzyme B: Functional relationships established for key mediators of apoptosis. J. Biol. Chem. 1997; 272: 17 907-11.
8. 8 Martelli AM, Bareggi R, Bortul R, Grill V, Narducci P, Zweyer M. The nuclear matrix and apoptosis. Histochem. Cell Biol. 1997; 108: 1-10.
9. 9 Trapani JA, Jans DA. Lymphocyte-mediated cytolysis: Dual apoptotic pathways with overlapping cytoplasmic and nuclear signalling pathways. In: Kumar S (ed.). Apoptosis: Biology, mechanisms and role in disease. Heidelberg: Springer-Verlag, 1998; 75-102.
10. 10 Hale AJ, Smith CA, Sutherland LC et al. Apoptosis: Molecular regulation of cell death. Eur. J. Biochem. 1996; 236: 1-26.
11. 11 Nicholson DW, Thornberry NA. Caspases: Killer proteases. Trends Biochem. Sci. 1997; 22: 299-306.
12. 12 Poe M, Blake JT, Boulton DA et al. Human cytotoxic lymphocyte granzyme B. J. Biol. Chem. 1991; 266: 98-103.
13. 13 Kumar S. The apoptotic cysteine protease CPP32. Int. J. Biochem. Cell Biol. 1997; 29: 393-6.
14. 14 Fernandes-Alnemri T, Armstrong RC, Krebs J et al. In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc. Natl Acad. Sci. USA. 1996; 93: 7464-9.
15. 15 Martin SJ, Green DR. Protease activation during apoptosis: Death by a thousand cuts? Cell 1995; 82: 349-52.
16. 16 Apasov S, Redegeld F, Sitkovsky M. Cell-mediated cytotoxicity: Contact and secreted factors. Curr. Opin. Immunol. 1993; 5: 404-10.
17. 17 Trapani JA. Target cell apoptosis induced by cytotoxic T cells and natural killer cells involves synergy between the poreforming protein, perforin, and the serine protease, granzyme B. Aust. N.Z. J. Med. 1995; 25: 793-9.
18. 18 Smyth MJ, Trapani JA. Granzymes: Exogenous proteinases that induce target cell apoptosis. Immunol. Today 1995; 16: 202-7.
19. 19 Jans DA, Jans P, Briggs LJ, Sutton V, Trapani JA. Nuclear transport of granzyme B (fragmentin-2)-dependence on perforin in vivo and cytosolic factors in vitro. J. Biol. Chem. 1996; 271: 30 781-9.
20. 20 Jans DA, Briggs LJ, Jans P et al. Nuclear targeting of the serine protease granzyme A (fragmentin-1). J. Cell Sci. 1998; 111: 2645-54.
21. 21 Jans DA, Sutton VR, Jans P, Froelich CJ, Trapani JA. Bcl-2 blocks perforin-induced nuclear translocation of granzymes, concomitant with protection against the nuclear events of apoptosis. J. Biol. Chem. 1998; 274: 3953-61.
22. 22 Trapani JA, Jans P, Smyth MJ et al. Perforin-dependent nuclear entry of granzyme B precedes apoptosis and is not a consequence of nuclear envelope dysfunction. Cell Death Differ. 1998; 5: 488-96.
23. 23 Shi L, Mai S, Israels S, Browne K, Trapani JA, Greenberg AH. Granzyme B (GraB) autonomously crosses the cell membrane and perforin initiates apoptosis and GraB nuclear localisation. J. Exp. Med. 1997; 185: 855-66.
24. 24 Trapani JA, Jans DA, Sutton V. Lymphocyte granule-mediated cell death. In: Vaux DA (ed.). Apoptosis and killer cell function. Geneva: Springer Seminars in Immunopathology, 1998; 19: 323-43.
25. 25 Liu C-C, Persechini PM, Young JD-E. Perforin and lymphocyte-mediated cytolysis. Immunol. Rev. 1995; 146: 145-75.
26. 26 Ortaldo JR, Winkler-Pickett RT, Nagishima K, Yagita H, Okumura K. Direct evidence for release of pore-forming protein during NK cellular lysis. J. Leukoc. Biol. 1992; 52: 483-8.
27. 27 Darmon AJ, Ehrman N, Caputo A, Fujinaga J, Bleackley RC. The cytotoxic T cell proteinase granzyme B does not activate Interleukin-1β-converting enzyme. J. Biol. Chem. 1994; 269: 32 043-6.
28. 28 Ebnet K, Hausmann M, Lehmann-Grube F et al. Granzyme A-deficient caspase 1 retain potent cell-mediated cytotoxicity. EMBO J. 1995; 17: 4230-9.
29. 29 Heusel JW, Wesselschmidt RL, Shresta S, Russell JH, Ley TJ. Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells. Cell 1994; 76: 977-87.
30. 30 Srinivasula SM, Fernandes-Alnemri T, Zangrilli J et al. The Ced-3/interleukin 1β converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2α are substrates for the apoptotic mediator CPP32. J. Biol. Chem. 1996; 271: 27 099-106.
31. 31 Sarin A, Williams MS, Alexander-Miller MA, Berzofsky JA, Zacharchuk CM, Henkart PA. Target cell lysis by CTL granule exocytosis is independent of ICE/Ced-3 family proteases. Immunity 1997; 6: 209-15.
32. 32 Trapani JA, Jans DA, Jans P, Smyth MJ, Browne KA, Sutton VR. Efficient nuclear targeting and the nuclear consequences of apoptosis induced by granzyme B and perforin are caspase-dependent, but cell death is caspase-independent. J. Biol. Chem. 1998; 273: 27 934-8.
33. 33 Froelich CJ, Hann WL, Poirer GG et al. Granzyme B/perforin-mediated apoptosis of Jurkat cells results in cleavage of poly (ADP-ribose) polymerase to the 89-kDa apoptotic fragment and less abundant 64-kDa fragment. Biochem. Biophys. Res. Comm. 1996; 227: 658-65.
34. 34 Song Q, Burrows SR, Smith G et al. Interleukin-1β-converting enzyme-like protease cleaves DNA-dependent protein kinase in cytotoxic T cell killing. J. Exp. Med. 1996; 184: 619-26.
35. 35 Andrade F, Roy S, Nicholson D, Thornberry N, Rosen A, Casciola-Rosen L. Granzyme B directly and efficiently cleaves several downstream caspase substrates: Implications for CTL-induced apoptosis. Immunity 1998; 8: 451-60.
36. 36 Beresford PJ, Kam C-M, Lieberman J. Recombinant human granzyme A binds to two putative III.A-associated proteins and cleaves one of them. Proc. Natl Acad. Sci. USA 1997; 94: 9285-90.
37. 37 Suidan HS, Bouvier J, Scheaerer E, Stone SR, Monard D, Tschopp J. Granzyme A released upon stimulation of cytotoxic T lymphocytes activates the thrombin receptor on neuronal cells and astrocytes. Proc. Natl Acad. Sci. USA 1994; 91: 8112-16.
38. 38 Shresta S, Goda P, Wesselschmidt R, Ley TJ. Residual cytotoxicity and granzyme K expression in granzyme A-deficient cytotoxic lymphocytes. J. Biol. Chem. 1997; 272: 20 236-44.
39. 39 Kagl D, Ledermann B, Burkl K et al. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 1994; 369: 31-7.
40. 40 Lowin B, Beermann F, Schmidt A, Tschopp J. A null mutation in the perforin gene impairs cytolytic T lymphocyte-and natural killer cell-mediated cytotoxicity. Proc. Natl Acad. Sci. USA 1994; 91; 11 571-5.
41. 41 Shresta S, MacIvor DM, Heusel JW, Russell JH, Ley TJ. Natural killer and lymphokine-activated killer cells require granzyme B for the rapid induction of apoptosis in susceptible target cells. Proc. Natl Acad. Sci. USA 1995; 92: 5679-83.
42. 42 Simon MM, Hausmann M, Tran T et al. In vitro-and ex vivo-derived eytolytic leukocytes from granzyme AxB double knockout mice are defective in granule-mediated apoptosis but not lysis of target cells. J. Exp. Med. 1997; 186: 1781-6.
43. 43 Froelich CJ, Orth K, Turbov J et al. New paradigm for lymphocyte granule-mediated cytotoxicity. Target cells bind and internalise granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis. J. Biol. Chem. 1996; 271: 29 073-9.
44. 44 Jans DA, Hübner S. Regulation of protein transport to the nucleus: Central role of phosphorylation. Physiol. Rev. 1996; 76: 651-85.
45. 45 Jans DA. Regulation of protein transport to the nucleus by phosphorylation. Biochem. J. 1995; 311: 705-16.
46. 46 Kalderon D, Richardson WD, Markham AF, Smith AE. Sequence requirements for nuclear location of simian virus 40 large-T antigen. Nature 1984; 311: 33-8.
47. 47 Kalderon D, Roberts BL, Richardson WD, Smith AE. A short amino acid sequence able to specify nuclear location. Cell 1984; 39: 499-509.
48. 48 Lanford RE, Butel JS. Construction and characterisation of an SV40 mutant defective in nuclear transport of T antigen. Cell 1984; 37: 801-13.
49. 49 Goerlich D, Vogel F, Mills AD, Hartmann E, Laskey RA. Distinct functions for the two importin subunits in nuclear protein import. Nature 1995; 377: 246-8.
50. 50 Imamoto N, Shimamoto T, Takao T et al. In vivo evidence for involvement of a 58 kDa component of nuclear pore-targeting complex in nuclear protein import. EMBO J. 1995; 15: 3617-26.
51. 51 Rexach M, Blobel G. Protein import into nuclei: Association and dissociation reactions involving transport substrate, transport factors, and nucleoporins. Cell 1995; 83: 683-92.
52. 52 Goerlich D, Pante N, Kutay U, Aebi U, Bischoff FR. Identification of different roles for RanGDP and RanGTP in nuclear protein import. EMBO J. 1996; 15: 5584-94.
53. 53 Moore MS, Blobel G. The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. Nature 1993; 365: 661-3.
54. 54 Goerlich D, Krostka S, Kraft R et al. Two different subunits of importin cooperate to recognise nuclear localisation signals and bind them to the nuclear envelope. Curr. Biol. 1995; 5: 383-92.
55. 55 Kutay U, Izaurralde E, Bischoff FR, Mattaj IW, Goerlich D. Dominant-negative mutants of importin-β block multiple pathways of import and export through the nuclear pore complex. EMBO J. 1997; 16: 1153-63.
56. 56 Goerlich D. Nuclear protein import. Curr. Opin. Cell Biol. 1997; 9: 412-19.
57. 57 Newmeyer DD, Forbes DJ. Nuclear import can be separated into distinct steps in vitro: Nuclear pore binding and translocation. Cell 1988; 52: 641-53.
58. 58 Richardson WD, Mills AD, Dilworth SM, Laskey RA, Dingwall D. Nuclear protein migration involves two steps: Rapid binding at the nuclear envelope followed by slower translocation through nuclear pores. Cell 1988; 52: 655-64.
59. 124 inhibits nuclear import of SV40 T-antigen proteins. J. Cell Biol. 1991; 115: 1203-12.
60. 3G-cap dependence of U3 and U2 snRNP transport. EMBO J. 1994; 13: 222-31.
61. 61 Akey CW. Visualization of transport-related configurations of the nuclear pore transporter. Biophys. J. 1990; 58: 341-55.
62. 62 Akey CW, Goldfarb DS. Protein import through the nuclear pore complex is a multistep process. J. Cell Biol. 1989; 109: 971-82.
63. 63 Schroder HC, Rottmann M, Bachmann M, Muller WEG. Purification and characterization of the major nucleoside triphosphatase from rat liver nuclear envelopes. J. Biol. Chem. 1986; 261: 663-8.
64. 64 Berrios M, Fisher PA, Matz EC. Localization of a myosin heavy chain-like polypeptide to Drosophila nuclear pore complexes. Proc. Natl Acad. Sci. USA 1991; 88: 219-23.
65. 312) enhances Dorsal nuclear import through facilitating nuclear localization sequence/importin interaction. J. Biol. Chem. 1998; 273: 22 745-52.
66. 66 Efthymiadis A, Shao H, Hübner S, Jans DA. Kinetic characterization of the human retinoblastoma protein bipartite nuclear localization sequence in vivo and in vitro: A comparison with the SV40 large T-antigen NLS. J. Biol. Chem. 1997; 272: 22 134-9.
67. 67 Lam M, Briggs LJ, Hu W, Martin J, Gillespic MT, Jans DA. Importin β recognises parathyroid hormone-related protein (PTHrP) with high affinity and mediates its nuclear import in the absence of importin α. J. Biol. Chem. 1999; 274: 7391-8.
68. 68 Chan CK, Hübner S, Hu W, Jans DA. Mutual exclusivity of DNA binding and nuclear localization signal recognition by the yeast transcription factor GAL4: Implications for non-viral DNA delivery. Gene Ther. 1998; 5: 1204-12.
69. 69 Fornerod M, Ohno M, Yoshida M, Mattaj IW. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 1997; 90: 1051-60.
70. 70 Siomi H, Dreyfuss G. A nuclear localisation domain in the hnRNP A1 protein. J. Cell Biol. 1995; 129: 551-60.
71. 71 Pollard VW, Michael WM, Nakielny S, Siomi MC, Wang F, Dreyfuss G. A novel receptor-mediated nuclear protein import pathway. Cell 1996; 86: 985-94.
72. 72 Jakel S, Goerlich D. Importin β, transportin, RanBP5 and RanBP7 mediate nuclear import of ribosomal proteins in mammalian cells. EMBO J. 1998; 15: 4491-502.
73. 73 Michael WM, Eder PS, Dreyfuss G. The K nuclear shuttling domain: A novel signal for nuclear import and nuclear export in the hnRNP K protein. EMBO J. 1997; 12: 3587-98.
74. 74 Fagotto F, Gluck U, Gumbiner BM. Nuclear localisation signal-independent and importin/karyopherin-independent nuclear import of β-catenin. Curr. Biol. 1998; 8: 181-90.
75. 75 Efthymiadis A, Briggs LJ, Jans DA. The HIV-1 Tat nuclear localisation sequence confers novel nuclear import properties. J. Biol. Chem. 1998; 273: 1623-8.
76. c-rel. Mol. Cell. Biol. 1991; 11: 5867-77.
77. 77 Lenardo MJ, Baltimore D. NF-kappa B: A pleiotropic mediator of inducible and tissue-specific gene control. Cell 1989; 58: 227-9.
78. 78 Norris JL, Manley JL. Selective nuclear transport of the Drosophila morphogen dorsal can be established by a signaling pathway involving the transmembrane protein Toll and protein kinase A. Genes Dev. 1992; 6: 1654-67.
79. 79 Pinkoski MJ, Winkler U, Hudig D, Bleackley RC. Binding of granzyme B in the nucleus of target cells: Recognition of an 80 kilodalton protein. J. Biol. Chem. 1996; 271: 10 225-9.
80. 80 Trapani JA, Browne KA, Smyth MJ, Jans DA. Localisation of granzyme B in the nucleus: A putative role in the mechanism of cytotoxic lymphocyte-mediated apoptosis. J. Biol. Chem. 1996; 271: 4127-33.
81. 81 Sutton V, Vaux DL, Trapani JA. Bcl-2 prevents apoptosis induced by perforin and granzyme B but not that mediated by whole cytotoxic lymphocytes. J. Immunol. 1997; 158: 5783-90.
82. 82 Nakajima H, Golstein P, Henkart PA. The target cell nucleus is not required for cell mediated granzyme-or Fas-based cytotoxicity. J. Exp. Med. 1995; 181: 1905-13.
83. 83 Nakayama K, Negishi I, Kuida K et al. Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice. Science 1993; 261: 1584-8.
84. 84 Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988; 335: 440-2.
85. 85 Chiu VK, Walsh CM, Liu C-C, Reed JC, Clark WR. Bcl-2 blocks degranulation but not fas-based cell-mediated cytotoxicity. J. Immunol. 1995; 154: 2023-32.
86. 86 Schroter M, Lowin B, Borner C, Tschopp J. Regulation of Fas (Apo-1/CD95)-and perforin-mediated lytic pathways of primary cytotoxic T lymphocytes by the protooncogene bcl-2. Eur. J. Immunol. 1995; 23: 3509-13.
87. 87 Strasser A, Harris AW, Huang D, Krammer PH, Cory S. Bcl-2 and fas/apo-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J. 1995; 14: 6136-47.
88. 88 Lacronique V, Mignon A, Fabre M et al. Bcl-2 protects from lethal hepatic apoptosis induced by an anti-fas antibody in mice. Nat. Med. 1996; 2: 80-6.
89. 89 Monaghan P, Robertson D, Amos TAS, Dyer MJS, Mason DY, Greaves ME. Ultrastructural localization of bcl-2 protein. J Histochem. Cytochem. 1992; 40: 1819-25.
90. 90 Krajewski S, Tanaka S, Takayama S, Schibler MJ, Fenton W, Reed JC. Investigation of the subcellular distribution of the bcl-2 oncoprotein residence in the nuclear envelope, endoplasmic reticulum and outer mitochondrial membranes. Cancer Res. 1993; 53: 4701-14.
91. 91 de Jong D, Prins DY, Reed JC, van Ommen GB, Kluin PM. Subcellular localization of the bcl-2 protein in malignant and normal lymphoid cells. Cancer Res. 1994; 54: 256-60.
92. 92 Muchmore SW, Sattler M, Liang H et al. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 1996; 381: 335-41.
93. 93 Greber UF, Gerace L. Depletion of calcium from the lumen of endoplasmic reticulum reversibly inhibits passive diffusion and signal-mediated transport into the nucleus. J. Cell Biol. 1995; 128: 5-14.
94. 2+ stores. Science 1996; 273: 1875-7.
95. 95 Ryan JJ, Prochownik E, Gotllieb CA et al. c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle. Proc. Natl Acad. Sci. USA 1994; 91: 5878-82.
96. 96 Meikrantz W, Gisselbrecht S, Tam SW, Schlegel R. Activation of cyclin A-dependent protein kinases during apoptosis. Proc. Natl Acad. Sci. USA 1994; 91, 3754-8.
97. 97 Pasternack MS, Bleier KJ, McInerney TN. Granzyme A binding to target cell proteins. Granzyme A binds to and cleaves nucleolin in vitro. J. Biol. Chem. 1991; 266: 14 703-8.
98. 98 Munger WE, Berrebi GA, Henkart PA. Possible involvement of CTL granule proteases in target cell DNA breakdown. Immunol. Rev. 1988; 103: 99-109.
99. 99 Hayes MP, Berrebi GA, Henkart PA. Induction of target cell DNA release by cytotoxic T lymphocyte granule protease granzyme A. J. Exp. Med. 1989; 170: 933-46.
100. 100 Liu X, Zou H, Slaughter C, Wang X. DFF, a heterodimeric protein that functions downstream of Caspase-3 to trigger DNA fragmentation during apoptosis. Cell 1997; 89: 175-84.
101. 101 Krajewski S, Gasgoyne RD, Zapata JM et al. Immunolocalization of the ICE/Ced-3-family protease, CPP32 (Caspase-3), in non-Hodgkin's lymphomas, chronic lymphocytic leukemias, and reactive lymph nodes. Blood 1997; 89: 3817-25.