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Gene Review

Gzmb  -  granzyme B

Mus musculus

Synonyms: AI553453, CCP-1/C11, CCP1, CTLA-1, Ctla-1, ...
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Disease relevance of Gzmb


High impact information on Gzmb


Chemical compound and disease context of Gzmb


Biological context of Gzmb

  • Granzyme B (GzmB) is a component of cytotoxic lymphocyte granules that can rapidly initiate apoptosis in target cells [11].
  • During granule-induced cell death, ROCK II cleavage by grB would overcome, for this apoptotic feature, the consequences of deficient caspase activation that may occur in virus-infected or malignant target cells [12].
  • Under these conditions, DNA fragmentation was not observed for at least 13 min, indicating nuclear accumulation of grB preceded the execution phase of apoptosis [13].
  • Furthermore, nuclear import of grB proceeded through an intact nuclear membrane, as the nuclei of cells whose cytoplasm was pre-loaded with 70 kDa FITC-dextran excluded dextran for up to 90 min while still undergoing apoptosis in response to perforin and grB [13].
  • Using a two-dimensional gel-based proteomics approach we have also examined the scale of granzyme B-initiated alterations to the proteome in the presence or absence of effector caspase-3 or -7 [14].

Anatomical context of Gzmb


Associations of Gzmb with chemical compounds


Enzymatic interactions of Gzmb

  • Granzyme C branched off first after the primate-rodent split and was involved in a recombination event with granzyme B before the rat-mouse divergence [21].
  • The study also demonstrates that M3R (which is restricted in expression to the peripheral autonomic organs) was efficiently cleaved by granzyme B (but not by caspases) at several sites, both in vitro and in intact cells [22].

Regulatory relationships of Gzmb

  • By Northern blot hybridization and functional assays, we found that IL-9 induced the expression of granzyme B in several T cell clones as well as in mast cell lines [23].
  • We have previously shown that perforin specifically induces the redistribution of cytoplasmic grB into the nucleus of dying cells, however a causal role for nuclear targeting of grB in cell death has not been demonstrated [13].
  • The mechanisms by which GrB induces cell death in Th1/Th2 effectors include both fratricide and suicide [24].
  • GrB-mediated killing was increased to a much greater extent when tumor cells expressed the eGFP-Smac fusion protein with a GrB cleavage site compared to a caspase 8 cleavage site [25].
  • Dependence of granzyme B-mediated cell death on a pathway regulated by Bcl-2 or its viral homolog, BHRF1 [26].

Other interactions of Gzmb


Analytical, diagnostic and therapeutic context of Gzmb


  1. Hyperthermia suppresses the cytotoxicity of NK cells via down-regulation of perforin/granzyme B expression. Koga, T., Harada, H., Shi, T.S., Okada, S., Suico, M.A., Shuto, T., Kai, H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  2. Resistance to granzyme B-mediated cytochrome c release in Bak-deficient cells. Wang, G.Q., Wieckowski, E., Goldstein, L.A., Gastman, B.R., Rabinovitz, A., Gambotto, A., Li, S., Fang, B., Yin, X.M., Rabinowich, H. J. Exp. Med. (2001) [Pubmed]
  3. Differential inhibition of the Fas- and granule-mediated cytolysis pathways by the orthopoxvirus cytokine response modifier A/SPI-2 and SPI-1 protein. Macen, J.L., Garner, R.S., Musy, P.Y., Brooks, M.A., Turner, P.C., Moyer, R.W., McFadden, G., Bleackley, R.C. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  4. A role for the granzyme B inhibitor serine protease inhibitor 6 in CD8+ memory cell homeostasis. Phillips, T., Opferman, J.T., Shah, R., Liu, N., Froelich, C.J., Ashton-Rickardt, P.G. J. Immunol. (2004) [Pubmed]
  5. Natural killer cell-mediated ablation of metastatic liver tumors by hydrodynamic injection of IFNalpha gene to mice. Takehara, T., Uemura, A., Tatsumi, T., Suzuki, T., Kimura, R., Shiotani, A., Ohkawa, K., Kanto, T., Hiramatsu, N., Hayashi, N. Int. J. Cancer (2007) [Pubmed]
  6. Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis. Motyka, B., Korbutt, G., Pinkoski, M.J., Heibein, J.A., Caputo, A., Hobman, M., Barry, M., Shostak, I., Sawchuk, T., Holmes, C.F., Gauldie, J., Bleackley, R.C. Cell (2000) [Pubmed]
  7. A family of serine esterases in lytic granules of cytolytic T lymphocytes. Masson, D., Tschopp, J. Cell (1987) [Pubmed]
  8. Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B. Darmon, A.J., Nicholson, D.W., Bleackley, R.C. Nature (1995) [Pubmed]
  9. The inducible cytotoxic T-lymphocyte-associated gene transcript CTLA-1 sequence and gene localization to mouse chromosome 14. Brunet, J.F., Dosseto, M., Denizot, F., Mattei, M.G., Clark, W.R., Haqqi, T.M., Ferrier, P., Nabholz, M., Schmitt-Verhulst, A.M., Luciani, M.F. Nature (1986) [Pubmed]
  10. Granzyme B is dispensable for immunologic tolerance to self in a murine model of systemic lupus erythematosus. Graham, K.L., Thibault, D.L., Steinman, J.B., Okeke, L., Kao, P.N., Utz, P.J. Arthritis Rheum. (2005) [Pubmed]
  11. DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis. Thomas, D.A., Du, C., Xu, M., Wang, X., Ley, T.J. Immunity (2000) [Pubmed]
  12. Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner. Sebbagh, M., Hamelin, J., Bertoglio, J., Solary, E., Bréard, J. J. Exp. Med. (2005) [Pubmed]
  13. Perforin-dependent nuclear entry of granzyme B precedes apoptosis, and is not a consequence of nuclear membrane dysfunction. Trapani, J.A., Jans, P., Smyth, M.J., Froelich, C.J., Williams, E.A., Sutton, V.R., Jans, D.A. Cell Death Differ. (1998) [Pubmed]
  14. Molecular ordering of the caspase activation cascade initiated by the cytotoxic T lymphocyte/natural killer (CTL/NK) protease granzyme B. Adrain, C., Murphy, B.M., Martin, S.J. J. Biol. Chem. (2005) [Pubmed]
  15. SPI-CI and SPI-6 cooperate in the protection from effector cell-mediated cytotoxicity. Bots, M., Kolfschoten, I.G., Bres, S.A., Rademaker, M.T., de Roo, G.M., Krüse, M., Franken, K.L., Hahne, M., Froelich, C.J., Melief, C.J., Offringa, R., Medema, J.P. Blood (2005) [Pubmed]
  16. Importance of leucine zipper domain of mi transcription factor (MITF) for differentiation of mast cells demonstrated using mi(ce)/mi(ce) mutant mice of which MITF lacks the zipper domain. Morii, E., Ogihara, H., Kim, D.K., Ito, A., Oboki, K., Lee, Y.M., Jippo, T., Nomura, S., Maeyama, K., Lamoreux, M.L., Kitamura, Y. Blood (2001) [Pubmed]
  17. Augmentation of effector CD8+ T cell generation with enhanced granzyme B expression by IL-27. Morishima, N., Owaki, T., Asakawa, M., Kamiya, S., Mizuguchi, J., Yoshimoto, T. J. Immunol. (2005) [Pubmed]
  18. Granzyme B activates procaspase-3 which signals a mitochondrial amplification loop for maximal apoptosis. Metkar, S.S., Wang, B., Ebbs, M.L., Kim, J.H., Lee, Y.J., Raja, S.M., Froelich, C.J. J. Cell Biol. (2003) [Pubmed]
  19. Requirement for aspartate-cleaved bid in apoptosis signaling by DNA-damaging anti-cancer regimens. Werner, A.B., Tait, S.W., de Vries, E., Eldering, E., Borst, J. J. Biol. Chem. (2004) [Pubmed]
  20. Inhibition of CPP32-like proteases prevents granzyme B- and Fas-, but not granzyme A-based cytotoxicity exerted by CTL clones. Anel, A., Gamen, S., Alava, M.A., Schmitt-Verhulst, A.M., Piñeiro, A., Naval, J. J. Immunol. (1997) [Pubmed]
  21. Isolation and complete structure of the lymphocyte serine protease granzyme G, a novel member of the granzyme multigene family in murine cytolytic T lymphocytes. Evolutionary origin of lymphocyte proteases. Jenne, D.E., Masson, D., Zimmer, M., Haefliger, J.A., Li, W.H., Tschopp, J. Biochemistry (1989) [Pubmed]
  22. Novel fragments of the Sjögren's syndrome autoantigens alpha-fodrin and type 3 muscarinic acetylcholine receptor generated during cytotoxic lymphocyte granule-induced cell death. Nagaraju, K., Cox, A., Casciola-Rosen, L., Rosen, A. Arthritis Rheum. (2001) [Pubmed]
  23. IL-9 induces expression of granzymes and high-affinity IgE receptor in murine T helper clones. Louahed, J., Kermouni, A., Van Snick, J., Renauld, J.C. J. Immunol. (1995) [Pubmed]
  24. Granzyme B, a new player in activation-induced cell death, is down-regulated by vasoactive intestinal peptide in Th2 but not Th1 effectors. Sharma, V., Delgado, M., Ganea, D. J. Immunol. (2006) [Pubmed]
  25. Targeting and amplification of immune killing of tumor cells by pro-Smac. Li, R., Rüttinger, D., Urba, W., Fox, B.A., Hu, H.M. Int. J. Cancer (2004) [Pubmed]
  26. Dependence of granzyme B-mediated cell death on a pathway regulated by Bcl-2 or its viral homolog, BHRF1. Davis, J.E., Sutton, V.R., Smyth, M.J., Trapani, J.A. Cell Death Differ. (2000) [Pubmed]
  27. Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis. Pardo, J., Bosque, A., Brehm, R., Wallich, R., Naval, J., Müllbacher, A., Anel, A., Simon, M.M. J. Cell Biol. (2004) [Pubmed]
  28. Mechanisms responsible for granzyme B-independent cytotoxicity. Shresta, S., Russell, J.H., Ley, T.J. Blood (1997) [Pubmed]
  29. Cytotoxic T lymphocyte-assisted suicide. Caspase 3 activation is primarily the result of the direct action of granzyme B. Atkinson, E.A., Barry, M., Darmon, A.J., Shostak, I., Turner, P.C., Moyer, R.W., Bleackley, R.C. J. Biol. Chem. (1998) [Pubmed]
  30. Bcl-2 prevents apoptosis induced by perforin and granzyme B, but not that mediated by whole cytotoxic lymphocytes. Sutton, V.R., Vaux, D.L., Trapani, J.A. J. Immunol. (1997) [Pubmed]
  31. Islet rejection in perforin-deficient mice: the role of perforin and Fas. Ahmed, K.R., Guo, T.B., Gaal, K.K. Transplantation (1997) [Pubmed]
  32. Proximity of the CTLA-1 serine esterase and Tcr alpha loci in mouse and man. Harper, K., Mattéi, M.G., Simon, D., Suzan, M., Guénet, J.L., Haddad, P., Sasportes, M., Golstein, P. Immunogenetics (1988) [Pubmed]
  33. Increased accuracy of renal allograft rejection diagnosis using combined perforin, granzyme B, and Fas ligand fine-needle aspiration immunocytology. Pascoe, M.D., Marshall, S.E., Welsh, K.I., Fulton, L.M., Hughes, D.A. Transplantation (2000) [Pubmed]
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