Granzyme A, which causes single-stranded DNA damage, targets the double-strand break repair protein Ku70

EMBO Reports

Volumn 7, Issue 4, 2006, Pages 431-437

  Zhu, Pengcheng ^a   Zhang, Dong ^a   Chowdhury, Dipanjan ^a   Martinvalet, Denis ^a   Keefe, Dennis ^a   Shi, Lianfa ^a   Lieberman, Judy ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Cytotoxic T lymphocyte; DNA repair; Granzyme A; Ku70

Indexed keywords

ARGININE; DOUBLE STRANDED DNA; GRANZYME A; KU ANTIGEN; PERFORIN; PROTEIN BAX; SINGLE STRANDED DNA;

APOPTOSIS; ARTICLE; CELL DEATH; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; DNA DAMAGE; DNA PROTEIN COMPLEX; GENE OVEREXPRESSION; GENE SILENCING; HUMAN; HUMAN CELL; MITOCHONDRION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN TRANSPORT; RNA INTERFERENCE;

ANIMALS; ANTIGENS, NUCLEAR; ARGININE; CELL NUCLEUS; CELLS, CULTURED; DNA; DNA DAMAGE; DNA REPAIR; DNA-BINDING PROTEINS; GENE EXPRESSION REGULATION; GRANZYMES; HUMANS; MEMBRANE GLYCOPROTEINS; MICE; PORE FORMING CYTOTOXIC PROTEINS; PROTEASE INHIBITORS; PROTEIN BINDING; SERINE ENDOPEPTIDASES; T-LYMPHOCYTES, CYTOTOXIC;

EID: 33645524585     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.1038/sj.embor.7400622     Document Type: Article

References (30)

1. Andrade F, Roy S, Nicholson D, Thornberry N, Rosen A, Casciola-Rosen L (1998) Granzyme B directly and efficiently cleaves several downstream caspase substrates: Implications for CTL-induced apoptosis. Immunity 8: 451-460
2. Bell JK, Goetz DH, Mahrus S, Harris JL, Fletterick RJ, Craik CS (2003) The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity. Nat Struct Biol 10: 527-534
3. Beresford PJ, Kam CM, Powers JC, Lieberman J (1997) Recombinant human granzyme A binds to two putative HLA-associated proteins and cleaves one of them. Proc Natl Acad Sci USA 94: 9285-9290
4. Beresford PJ, Xia Z, Greenberg AH, Lieberman J (1999) Granzyme A loading induces rapid cytolysis and a novel form of DNA damage independently of caspase activation. Immunity 10: 585-594
5. Beresford PJ, Zhang D, Oh DY, Fan Z, Greer EL, Russo ML, Jaju M, Lieberman J (2001) Granzyme A activates an endoplasmic reticulum-associated caspase-independent nuclease to induce single-stranded DNA nicks. J Biol Chem 276: 43285-43293
6. Bredemeyer AJ, Lewis RM, Malone JP, Davis AE, Gross J, Townsend RR, Ley TJ (2004) A proteomic approach for the discovery of protease substrates. Proc Natl Acad Sci USA 101: 11785-11790
7. Downs JA, Jackson SP (2004) A means to a DNA end: The many roles of Ku. Nat Rev Mol Cell Biol 5: 367-378
8. Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J (2003a) Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell 112: 659-672
9. Fan Z, Beresford PJ, Zhang D, Xu Z, Novina CD, Yoshida A, Pommier Y, Lieberman J (2003b) Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol 4: 145-153
10. Gell D, Jackson SP (1999) Mapping of protein-protein interactions within the DNA-dependent protein kinase complex. Nucleic Acids Res 27: 3494-3502
11. Heibein JA, Goping IS, Barry M, Pinkoski MJ, Shore GC, Green DR, Bleackley RC (2000) Granzyme B-mediated cytochrome c release is regulated by the bcl-2 family members bid and Bax. J Exp Med 192: 1391-1402
12. Hink-Schauer C, Estebanez-Perpina E, Kurschus FC, Bode W, Jenne DE (2003) Crystal structure of the apoptosis-inducing human granzyme A dimer. Nat Struct Biol 10: 535-540
13. Jones JM, Gellert M, Yang W (2001) A Ku bridge over broken DNA. Structure (Camb) 9: 881-884
14. Lieberman J (2003) Cell death and immunity: The ABCs of granule-mediated cytotoxicity: New weapons in the arsenal. Nat Rev Immunol 3: 361-370
15. Lieberman J, Fan Z (2003) Nuclear war: The granzyme A-bomb. Curr Opin Immunol 15: 553-559
16. Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC (2003) Granzyme B: A natural born killer. Immunol Rev 193: 31-38
17. Martinvalet D, Zhu P, Lieberman J (2005) Granzyme A induces caspase-independent mitochondrial damage, a required first step for apoptosis. Immunity 22: 355-370
18. Mimori T, Akizuki M, Yamagata H, Inada S, Yoshida S, Homma M (1981) Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis-scleroderma overlap. J Clin Invest 68: 611-620
19. Morozov VE, Falzon M, Anderson CW, Kuff EL (1994) DNA-dependent protein kinase is activated by nicks and larger single-stranded gaps. J Biol Chem 269: 16684-16688
20. Pardo J, Bosque A, Brehm R, Wallich R, Naval J, Mullbacher A, Anel A, Simon MM (2004) Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis. J Cell Biol 167: 457-468
21. Pasternack MS, Bleier KJ, McInerney TN (1991) Granzyme A binding to target cell proteins. Granzyme A binds to and cleaves nucleolin in vitro. J Biol Chem 266: 14703-14708
22. Pham CT, MacIvor DM, Hug BA, Heusel JW, Ley TJ (1996) Long-range disruption of gene expression by a selectable marker cassette. Proc Natl Acad Sci USA 93: 13090-13095
23. Pircher H, Burki K, Lang R, Hengartner H, Zinkernagel RM (1989) Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342: 559-561
24. Rosen A, Casciola-Rosen L (1999) Autoantigens as substrates for apoptotic proteases: Implications for the pathogenesis of systemic autoimmune disease. Cell Death Differ 6: 6-12
25. Sawada M, Sun W, Hayes P, Leskov K, Boothman DA, Matsuyama S (2003) Ku70 suppresses the apoptotic translocation of Bax to mitochondria. Nat Cell Biol 5: 320-329
26. Shresta S, Graubert TA, Thomas DA, Raptis SZ, Ley TJ (1999) Granzyme A initiates an alternative pathway for granule-mediated apoptosis. Immunity 10: 595-605
27. Thomas DA, Scorrano L, Putcha GV, Korsmeyer SJ, Ley TJ (2001) Granzyme B can cause mitochondrial depolarization and cell death in the absence of BID, BAX, and BAK. Proc Natl Acad Sci USA 98: 14985-14990
28. Torrance H, Giffin W, Rodda DJ, Pope L, Hache RJ (1998) Sequence-specific binding of Ku autoantigen to single-stranded DNA. J Biol Chem 273: 20810-20819
29. Walker JR, Corpina RA, Goldberg J (2001) Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412: 607-614
30. Xia Z, Kam CM, Huang C, Powers JC, Mandle RJ, Stevens RL, Lieberman J (1998) Expression and purification of enzymatically active recombinant granzyme B in a baculovirus system. Biochem Biophys Res Commun 243: 384-389