A Quarter Century of Granzymes

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2011 Nov 5

PMID 22052191

Citations 83

Authors

C L Ewen

K P Kane

R C Bleackley

Affiliations

Soon will be listed here.

Abstract

Granzymes (Grs) were discovered just over a quarter century ago. They are produced by cytotoxic T cells and natural killer cells and are released upon interaction with target cells. Intensive biochemical, genetic, and biological studies have been performed in order to study their roles in immunity and inflammation. This review summarizes research on the family of Grs.

Citing Articles

Contradictory Mechanisms of rheumatoid arthritis and hepatitis B virus infection activation.

Zhu F, Wang M, Zhang X, Zhao G, Gao H, Zhou L Heliyon. 2025; 11(1):e41444.

PMID: 39850429 PMC: 11755052. DOI: 10.1016/j.heliyon.2024.e41444.

Granzyme B Promotes Proliferation, Migration and EMT Process in Gastric Cancer.

Lu Z, Huang X, Shen Q, Chen E, Feng Y Biochem Genet. 2024; .

PMID: 38801462 DOI: 10.1007/s10528-024-10841-2.

Extended Cleavage Specificity of two Hematopoietic Serine Proteases from a Ray-Finned Fish, the Spotted Gar ().

Valentini P, Akula S, Alvarado-Vazquez A, Hallgren J, Fu Z, Racicot B Int J Mol Sci. 2024; 25(3).

PMID: 38338947 PMC: 10855939. DOI: 10.3390/ijms25031669.

Decoding the mechanisms of chimeric antigen receptor (CAR) T cell-mediated killing of tumors: insights from granzyme and Fas inhibition.

Montalvo M, Bandey I, Rezvan A, Wu K, Saeedi A, Kulkarni R Cell Death Dis. 2024; 15(2):109.

PMID: 38307835 PMC: 10837176. DOI: 10.1038/s41419-024-06461-8.

Combined Role of Interleukin-15 Stimulated Natural Killer Cell-Derived Extracellular Vesicles and Carboplatin in Osimertinib-Resistant H1975 Lung Cancer Cells with EGFR Mutations.

Nathani A, Sun L, Khan I, Aare M, Bagde A, Li Y Pharmaceutics. 2024; 16(1).

PMID: 38258094 PMC: 10821370. DOI: 10.3390/pharmaceutics16010083.

References

Goping I, Sawchuk T, Underhill D, Bleackley R . Identification of {alpha}-tubulin as a granzyme B substrate during CTL-mediated apoptosis. J Cell Sci. 2006; 119(Pt 5):858-65. DOI: 10.1242/jcs.02791. View

Sutton V, Davis J, Cancilla M, Johnstone R, Ruefli A, Sedelies K . Initiation of apoptosis by granzyme B requires direct cleavage of bid, but not direct granzyme B-mediated caspase activation. J Exp Med. 2000; 192(10):1403-14. PMC: 2193191. DOI: 10.1084/jem.192.10.1403. View

Shi L, Kam C, POWERS J, Aebersold R, Greenberg A . Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. J Exp Med. 1992; 176(6):1521-9. PMC: 2119451. DOI: 10.1084/jem.176.6.1521. View

Zhu P, Zhang D, Chowdhury D, Martinvalet D, Keefe D, Shi L . Granzyme A, which causes single-stranded DNA damage, targets the double-strand break repair protein Ku70. EMBO Rep. 2006; 7(4):431-7. PMC: 1456912. DOI: 10.1038/sj.embor.7400622. View

Tak P, Kraan M, Breedveld F, Froelich C, Hack C . The levels of soluble granzyme A and B are elevated in plasma and synovial fluid of patients with rheumatoid arthritis (RA). Clin Exp Immunol. 1999; 116(2):366-70. PMC: 1905268. DOI: 10.1046/j.1365-2249.1999.00881.x. View

van de Craen M, Van den brande I, Declercq W, Irmler M, Beyaert R, Tschopp J . Cleavage of caspase family members by granzyme B: a comparative study in vitro. Eur J Immunol. 1997; 27(5):1296-9. DOI: 10.1002/eji.1830270535. View

Heibein J, Goping I, Barry M, Pinkoski M, Shore G, Green D . Granzyme B-mediated cytochrome c release is regulated by the Bcl-2 family members bid and Bax. J Exp Med. 2000; 192(10):1391-402. PMC: 2193181. DOI: 10.1084/jem.192.10.1391. View

Martinvalet D, Dykxhoorn D, Ferrini R, Lieberman J . Granzyme A cleaves a mitochondrial complex I protein to initiate caspase-independent cell death. Cell. 2008; 133(4):681-92. PMC: 2840390. DOI: 10.1016/j.cell.2008.03.032. View

Froelich C, Hanna W, Poirier G, Duriez P, DAmours D, Salvesen G . 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 Commun. 1996; 227(3):658-65. DOI: 10.1006/bbrc.1996.1565. View

10.

Lobe C, Finlay B, Paranchych W, Paetkau V, Bleackley R . Novel serine proteases encoded by two cytotoxic T lymphocyte-specific genes. Science. 1986; 232(4752):858-61. DOI: 10.1126/science.3518058. View

11.

Hua G, Zhang Q, Fan Z . Heat shock protein 75 (TRAP1) antagonizes reactive oxygen species generation and protects cells from granzyme M-mediated apoptosis. J Biol Chem. 2007; 282(28):20553-60. DOI: 10.1074/jbc.M703196200. View

12.

Zhang D, Beresford P, Greenberg A, Lieberman J . Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis. Proc Natl Acad Sci U S A. 2001; 98(10):5746-51. PMC: 33284. DOI: 10.1073/pnas.101329598. View

13.

Masson D, Nabholz M, Estrade C, Tschopp J . Granules of cytolytic T-lymphocytes contain two serine esterases. EMBO J. 1986; 5(7):1595-600. PMC: 1166984. DOI: 10.1002/j.1460-2075.1986.tb04401.x. View

14.

Brunet J, Dosseto M, Denizot F, Mattei M, Clark W, Haqqi T . The inducible cytotoxic T-lymphocyte-associated gene transcript CTLA-1 sequence and gene localization to mouse chromosome 14. Nature. 1986; 322(6076):268-71. DOI: 10.1038/322268a0. View

15.

Cullen S, Afonina I, Donadini R, Luthi A, Medema J, Bird P . Nucleophosmin is cleaved and inactivated by the cytotoxic granule protease granzyme M during natural killer cell-mediated killing. J Biol Chem. 2008; 284(8):5137-47. DOI: 10.1074/jbc.M807913200. View

16.

Joeckel L, Wallich R, MARTIN P, Sanchez-Martinez D, Weber F, Martin S . Mouse granzyme K has pro-inflammatory potential. Cell Death Differ. 2011; 18(7):1112-9. PMC: 3131959. DOI: 10.1038/cdd.2011.5. View

17.

Lobe C, Havele C, Bleackley R . Cloning of two genes that are specifically expressed in activated cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1986; 83(5):1448-52. PMC: 323093. DOI: 10.1073/pnas.83.5.1448. View

18.

Medema J, Toes R, Scaffidi C, Zheng T, Flavell R, Melief C . Cleavage of FLICE (caspase-8) by granzyme B during cytotoxic T lymphocyte-induced apoptosis. Eur J Immunol. 1998; 27(12):3492-8. DOI: 10.1002/eji.1830271250. View

19.

Jenne D, Rey C, Haefliger J, Qiao B, Groscurth P, Tschopp J . Identification and sequencing of cDNA clones encoding the granule-associated serine proteases granzymes D, E, and F of cytolytic T lymphocytes. Proc Natl Acad Sci U S A. 1988; 85(13):4814-8. PMC: 280526. DOI: 10.1073/pnas.85.13.4814. View

20.

Johnson H, Scorrano L, Korsmeyer S, Ley T . Cell death induced by granzyme C. Blood. 2003; 101(8):3093-101. DOI: 10.1182/blood-2002-08-2485. View