| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 43, 27934-27938, October 23, 1998
,,, and
From the The secretory lysosomes of cytolytic lymphocytes
house the principal apoptotic molecules for eliminating virus-infected
cells: a membranolytic agent, perforin, and the serine protease,
granzyme B. Perforin allows granzyme B access to cytosolic and nuclear substrates that, when cleaved, result in the characteristic apoptotic phenotype. Key among these substrates is a family of cytoplasmic caspases that mediate cell suicide. We have examined the caspase dependence of several nuclear and cytoplasmic parameters of apoptosis induced by purified perforin and granzyme B. Cell membrane leakage in
response to perforin and granzyme B was independent of caspase activation; however, nuclear events such as DNA fragmentation and
nuclear condensation and disintegration were abolished by the
broad-acting caspase inhibitor, z-VAD-fmk. Despite being spared from
nuclear damage, z-VAD-fmk-treated cells exposed to both cytotoxins uniformly died when they were re-cultured, while cells exposed to
perforin or granzyme alone survived and proliferated as readily as
untreated cells. Pretreatment of cells with z-VAD-fmk also resulted in
reduced granzyme B nuclear uptake following addition of perforin;
however, its uptake into the cytoplasm in the absence of perforin was
unaffected. We conclude that cell death in response to perforin and
granzyme B does not require caspase activation and still proceeds
efficiently through non-nuclear pathways when nuclear substrate
cleavage is inhibited.
The John Connell Laboratory, The
Austin Research Institute, Studley Road, Heidelberg 3084, Australia and
the ¶ Nuclear Targeting Laboratory, Division of Biochemistry and
Molecular Biology, John Curtin School of Medical Research, P. O. Box
334, Canberra City 2601, Australia
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Meslin, J. Thiery, C. Richon, A. Jalil, and S. Chouaib Granzyme B-induced Cell Death Involves Induction of p53 Tumor Suppressor Gene and Its Activation in Tumor Target Cells J. Biol. Chem., November 9, 2007; 282(45): 32991 - 32999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Hostetter, C. R. K. Loeb, F. Chu, and C. S. Craik Hip Is a Pro-survival Substrate of Granzyme B J. Biol. Chem., September 21, 2007; 282(38): 27865 - 27874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Z. Packard, W. G. Telford, A. Komoriya, and P. A. Henkart Granzyme B Activity in Target Cells Detects Attack by Cytotoxic Lymphocytes J. Immunol., September 15, 2007; 179(6): 3812 - 3820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. R. Sutton, N. J. Waterhouse, K. A. Browne, K. Sedelies, A. Ciccone, D. Anthony, A. Koskinen, A. Mullbacher, and J. A. Trapani Residual active granzyme B in cathepsin C-null lymphocytes is sufficient for perforin-dependent target cell apoptosis J. Cell Biol., February 12, 2007; 176(4): 425 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Bredemeyer, P. E. Carrigan, T. A. Fehniger, D. F. Smith, and T. J. Ley Hop Cleavage and Function in Granzyme B-induced Apoptosis J. Biol. Chem., December 1, 2006; 281(48): 37130 - 37141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Lawrence, A. Kadioglu, A.-L. Yang, W. R. Coward, and S. C. Chow The Cathepsin B Inhibitor, z-FA-FMK, Inhibits Human T Cell Proliferation In Vitro and Modulates Host Response to Pneumococcal Infection In Vivo J. Immunol., September 15, 2006; 177(6): 3827 - 3836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Estella, M. D. McKenzie, T. Catterall, V. R. Sutton, P. I. Bird, J. A. Trapani, T. W. Kay, and H. E. Thomas Granzyme B-Mediated Death of Pancreatic {beta}-Cells Requires the Proapoptotic BH3-Only Molecule Bid. Diabetes, August 1, 2006; 55(8): 2212 - 2219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wang, R. Allie, K. Conant, N. Haughey, J. Turchan-Chelowo, K. Hahn, A. Rosen, J. Steiner, S. Keswani, M. Jones, et al. Granzyme B mediates neurotoxicity through a G-protein-coupled receptor FASEB J, June 1, 2006; 20(8): 1209 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Waterhouse, V. R. Sutton, K. A Sedelies, A. Ciccone, M. Jenkins, S. J. Turner, P. I. Bird, and J. A. Trapani Cytotoxic T lymphocyte-induced killing in the absence of granzymes A and B is unique and distinct from both apoptosis and perforin-dependent lysis. J. Cell Biol., April 10, 2006; 173(1): 133 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Adrain, P. J. Duriez, G. Brumatti, P. Delivani, and S. J. Martin The Cytotoxic Lymphocyte Protease, Granzyme B, Targets the Cytoskeleton and Perturbs Microtubule Polymerization Dynamics J. Biol. Chem., March 24, 2006; 281(12): 8118 - 8125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Goping, T. Sawchuk, D. A. Underhill, and R. C. Bleackley Identification of {alpha}-tubulin as a granzyme B substrate during CTL-mediated apoptosis. J. Cell Sci., March 1, 2006; 119(Pt 5): 858 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sebbagh, J. Hamelin, J. Bertoglio, E. Solary, and J. Breard Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner J. Exp. Med., February 7, 2005; 201(3): 465 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pardo, A. Bosque, R. Brehm, R. Wallich, J. Naval, A. Mullbacher, A. Anel, and M. M. Simon Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis J. Cell Biol., November 8, 2004; 167(3): 457 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Bredemeyer, R. M. Lewis, J. P. Malone, A. E. Davis, J. Gross, R. R. Townsend, and T. J. Ley A proteomic approach for the discovery of protease substrates PNAS, August 10, 2004; 101(32): 11785 - 11790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, L. H. Cheung, W. N. Hittelman, and M. G. Rosenblum Targeted delivery of human pro-apoptotic enzymes to tumor cells: In vitro studies describing a novel class of recombinant highly cytotoxic agents Mol. Cancer Ther., December 1, 2003; 2(12): 1341 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, L. H. Cheung, P. Thorpe, and M. G. Rosenblum Mechanistic studies of a novel human fusion toxin composed of vascular endothelial growth factor (VEGF)121 and the serine protease granzyme B: Directed apoptotic events in vascular endothelial cells Mol. Cancer Ther., October 1, 2003; 2(10): 949 - 959. [Abstract] [Full Text]
|
|
|
|
|
|
C. A. Belmokhtar, J. Hillion, C. Dudognon, S. Fiorentino, M. Flexor, M. Lanotte, and E. Segal-Bendirdjian Apoptosome-independent Pathway for Apoptosis: BIOCHEMICAL ANALYSIS OF APAF-1 DEFECTS AND BIOLOGICAL OUTCOMES J. Biol. Chem., August 8, 2003; 278(32): 29571 - 29580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. McIlroy, P.-F. Cartron, P. Tuffery, Y. Dudoit, A. Samri, B. Autran, F. M. Vallette, P. Debre, and I. Theodorou A triple-mutated allele of granzyme B incapable of inducing apoptosis PNAS, March 4, 2003; 100(5): 2562 - 2567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Trapani, V. R. Sutton, K. Y.T. Thia, Y. Q. Li, C. J. Froelich, D. A. Jans, M. S. Sandrin, and K. A. Browne A clathrin/dynamin- and mannose-6-phosphate receptor-independent pathway for granzyme B-induced cell death J. Cell Biol., January 21, 2003; 160(2): 223 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Preston, C. S. Zarella, W. F. Pendergraft III, E. H. Rudolph, J. J. Yang, S. B. Sekura, J. C. Jennette, and R. J. Falk Novel Effects of Neutrophil-Derived Proteinase 3 and Elastase on the Vascular Endothelium Involve In Vivo Cleavage of NF-{kappa}B and Proapoptotic Changes in JNK, ERK, and p38 MAPK Signaling Pathways J. Am. Soc. Nephrol., December 1, 2002; 13(12): 2840 - 2849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Wieckowski, G.-Q. Wang, B. R. Gastman, L. A. Goldstein, and H. Rabinowich Granzyme B-mediated Degradation of T-Cell Receptor {zeta} Chain Cancer Res., September 1, 2002; 62(17): 4884 - 4889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Hirst, M. S. Buzza, V. R. Sutton, J. A. Trapani, K. L. Loveland, and P. I. Bird Perforin-independent expression of granzyme B and proteinase inhibitor 9 in human testis and placenta suggests a role for granzyme B-mediated proteolysis in reproduction Mol. Hum. Reprod., December 1, 2001; 7(12): 1133 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-Q. Wang, E. Wieckowski, L. A. Goldstein, B. R. Gastman, A. Rabinovitz, A. Gambotto, S. Li, B. Fang, X.-M. Yin, and H. Rabinowich Resistance to Granzyme B-mediated Cytochrome c Release in Bak-deficient Cells J. Exp. Med., November 5, 2001; 194(9): 1325 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Jerome, Z. Chen, R. Lang, M. R. Torres, J. Hofmeister, S. Smith, R. Fox, C. J. Froelich, and L. Corey HSV and Glycoprotein J Inhibit Caspase Activation and Apoptosis Induced by Granzyme B or Fas J. Immunol., October 1, 2001; 167(7): 3928 - 3935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Ruefli, M. J. Ausserlechner, D. Bernhard, V. R. Sutton, K. M. Tainton, R. Kofler, M. J. Smyth, and R. W. Johnstone The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species PNAS, September 4, 2001; (2001) 191208598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Smyth, J. M. Kelly, V. R. Sutton, J. E. Davis, K. A. Browne, T. J. Sayers, and J. A. Trapani Unlocking the secrets of cytotoxic granule proteins J. Leukoc. Biol., July 1, 2001; 70(1): 18 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. R. Sutton, J. E. Davis, M. Cancilla, R. W. Johnstone, A. A. Ruefli, K. Sedelies, K. A. Browne, and J. A. Trapani Initiation of Apoptosis by Granzyme B Requires Direct Cleavage of Bid, but Not Direct Granzyme B-mediated Caspase Activation J. Exp. Med., November 13, 2000; 192(10): 1403 - 1414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Chu, W. G. Wierda, and T. J. Kipps CD40 activation does not protect chronic lymphocytic leukemia B cells from apoptosis induced by cytotoxic T lymphocytes Blood, June 15, 2000; 95(12): 3853 - 3858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-F. Eléouët, E. A. Slee, F. Saurini, N. Castagné, D. Poncet, C. Garrido, E. Solary, and S. J. Martin The Viral Nucleocapsid Protein of Transmissible Gastroenteritis Coronavirus (TGEV) Is Cleaved by Caspase-6 and -7 during TGEV-Induced Apoptosis J. Virol., May 1, 2000; 74(9): 3975 - 3983. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. E. Jones, C. R. Lo, H. Liu, Z. Pradhan, L. Garcia, A. Srinivasan, K. L. Valentino, and M. J. Czaja Role of caspases and NF-kappa B signaling in hydrogen peroxide- and superoxide-induced hepatocyte apoptosis Am J Physiol Gastrointest Liver Physiol, May 1, 2000; 278(5): G693 - G699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Ruefli, M. J. Smyth, and R. W. Johnstone HMBA induces activation of a caspase-independent cell death pathway to overcome P-glycoprotein-mediated multidrug resistance Blood, April 1, 2000; 95(7): 2378 - 2385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhou, A. Zhao, G. Goping, and P. Hirszel Gliotoxin-Induced Cytotoxicity Proceeds via Apoptosis and Is Mediated by Caspases and Reactive Oxygen Species in LLC-PK1 Cells Toxicol. Sci., March 1, 2000; 54(1): 194 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Jones, C. R. Lo, H. Liu, A. Srinivasan, K. Streetz, K. L. Valentino, and M. J. Czaja Hepatocytes Sensitized to Tumor Necrosis Factor-alpha Cytotoxicity Undergo Apoptosis through Caspase-dependent and Caspase-independent Pathways J. Biol. Chem., January 7, 2000; 275(1): 705 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Browne, E. Blink, V. R. Sutton, C. J. Froelich, D. A. Jans, and J. A. Trapani Cytosolic Delivery of Granzyme B by Bacterial Toxins: Evidence that Endosomal Disruption, in Addition to Transmembrane Pore Formation, Is an Important Function of Perforin Mol. Cell. Biol., December 1, 1999; 19(12): 8604 - 8615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mullbacher, P. Waring, R. Tha Hla, T. Tran, S. Chin, T. Stehle, C. Museteanu, and M. M. Simon Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes PNAS, November 23, 1999; 96(24): 13950 - 13955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Kolenko, R. G. Uzzo, R. Bukowski, N. H. Bander, A. C. Novick, E. D. Hsi, and J. H. Finke Dead or Dying: Necrosis versus Apoptosis in Caspase-deficient Human RenalCell Carcinoma Cancer Res., June 1, 1999; 59(12): 2838 - 2842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Jans, V. R. Sutton, P. Jans, C. J. Froelich, and J. A. Trapani BCL-2 Blocks Perforin-induced Nuclear Translocation of Granzymes Concomitant with Protection against the Nuclear Events of Apoptosis J. Biol. Chem., February 12, 1999; 274(7): 3953 - 3961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. MILLER Activation of Apoptosis and Its Inhibition Ann. N.Y. Acad. Sci., January 1, 1999; 886(1): 132 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Browne, R. W. Johnstone, D. A. Jans, and J. A. Trapani Filamin (280-kDa Actin-binding Protein) Is a Caspase Substrate and Is Also Cleaved Directly by the Cytotoxic T Lymphocyte Protease Granzyme B during Apoptosis J. Biol. Chem., December 8, 2000; 275(50): 39262 - 39266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Ruefli, M. J. Ausserlechner, D. Bernhard, V. R. Sutton, K. M. Tainton, R. Kofler, M. J. Smyth, and R. W. Johnstone The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species PNAS, September 11, 2001; 98(19): 10833 - 10838. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
