HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 21, 22236-22242, May 21, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/21/22236    most recent M401670200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kelly, J. M. Articles by Smyth, M. J. Search for Related Content PubMed PubMed Citation Articles by Kelly, J. M. Articles by Smyth, M. J. Social Bookmarking                      What's this?

Granzyme M Mediates a Novel Form of Perforin-dependent Cell Death^*

Janice M. Kelly, Nigel J. Waterhouse, Erika Cretney, Kylie A. Browne, Sarah Ellis, Joseph A. Trapani, and Mark J. Smyth¶

From the Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, 8006 Victoria, Australia

Cell death is mediated by cytotoxic lymphocytes through various granule serine proteases released with perforin. The unique protease activity, restricted expression, and distinct gene locus of granzyme M suggested this enzyme might have a novel biological function or trigger a novel form of cell death. Herein, we demonstrate that in the presence of perforin, the protease activity of granzyme M rapidly and effectively induces target cell death. In contrast to granzyme B, cell death induced by granzyme M does not feature obvious DNA fragmentation, occurs independently of caspases, caspase activation, and perturbation of mitochondria and is not inhibited by overexpression of Bcl-2. These data raise the likelihood that granzyme M represents a third major and specialized perforin-dependent cell death pathway that plays a significant role in death mediated by NK cells.

Received for publication, February 16, 2004 , and in revised form, March 12, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

A Peter Doherty Fellow of the National Health and Medical Research Council of Australia.

Currently supported by National Health and Medical Research Council of Australia Research fellowships and a Program Grant.

^¶ To whom correspondence should be addressed. Tel.: 61-3-9656-3728; Fax: 61-3-9656-1411; E-mail: m.smyth{at}pmci.unimelb.edu.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Bovenschen, P. J. A. de Koning, R. Quadir, R. Broekhuizen, J. M. A. Damen, C. J. Froelich, M. Slijper, and J. A. Kummer NK Cell Protease Granzyme M Targets {alpha}-Tubulin and Disorganizes the Microtubule Network J. Immunol., June 15, 2008; 180(12): 8184 - 8191. [Abstract] [Full Text] [PDF]

				E. Fellows, S. Gil-Parrado, D. E. Jenne, and F. C. Kurschus Natural killer cell-derived human granzyme H induces an alternative, caspase-independent cell-death program Blood, July 15, 2007; 110(2): 544 - 552. [Abstract] [Full Text] [PDF]

				G. Hua, Q. Zhang, and Z. Fan Heat Shock Protein 75 (TRAP1) Antagonizes Reactive Oxygen Species Generation and Protects Cells from Granzyme M-mediated Apoptosis J. Biol. Chem., July 13, 2007; 282(28): 20553 - 20560. [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]

				M. Bots and J. P. Medema Granzymes at a glance J. Cell Sci., December 15, 2006; 119(24): 5011 - 5014. [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]

				H. Lu, Q. Hou, T. Zhao, H. Zhang, Q. Zhang, L. Wu, and Z. Fan Granzyme M Directly Cleaves Inhibitor of Caspase-Activated DNase (CAD) to Unleash CAD Leading to DNA Fragmentation J. Immunol., July 15, 2006; 177(2): 1171 - 1178. [Abstract] [Full Text] [PDF]

				R. Godal, U. Keilholz, L. Uharek, A. Letsch, A. M. Asemissen, A. Busse, I.-K. Na, E. Thiel, and C. Scheibenbogen Lymphomas are sensitive to perforin-dependent cytotoxic pathways despite expression of PI-9 and overexpression of bcl-2 Blood, April 15, 2006; 107(8): 3205 - 3211. [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]

				R. Ravi, E. J. Fuchs, A. Jain, V. Pham, K. Yoshimura, T. Prouser, S. Jalla, X. Zhou, E. Garrett-Mayer, S. H. Kaufmann, et al. Resistance of Cancers to Immunologic Cytotoxicity and Adoptive Immunotherapy via X-Linked Inhibitor of Apoptosis Protein Expression and Coexisting Defects in Mitochondrial Death Signaling Cancer Res., February 1, 2006; 66(3): 1730 - 1739. [Abstract] [Full Text] [PDF]

				B. Bade, H. E. Boettcher, J. Lohrmann, C. Hink-Schauer, K. Bratke, D. E. Jenne, J. C. Virchow Jr, and W. Luttmann Differential expression of the granzymes A, K and M and perforin in human peripheral blood lymphocytes Int. Immunol., November 1, 2005; 17(11): 1419 - 1428. [Abstract] [Full Text] [PDF]

				L. I. Pao, N. Sumaria, J. M. Kelly, S. v. Dommelen, E. Cretney, M. E. Wallace, D. A. Anthony, A. P. Uldrich, D. I. Godfrey, J. M. Papadimitriou, et al. Functional Analysis of Granzyme M and Its Role in Immunity to Infection J. Immunol., September 1, 2005; 175(5): 3235 - 3243. [Abstract] [Full Text] [PDF]

				L. Shi, D. Keefe, E. Durand, H. Feng, D. Zhang, and J. Lieberman Granzyme B Binds to Target Cells Mostly by Charge and Must Be Added at the Same Time as Perforin to Trigger Apoptosis J. Immunol., May 1, 2005; 174(9): 5456 - 5461. [Abstract] [Full Text] [PDF]

				I. Voskoboinik, M.-C. Thia, J. Fletcher, A. Ciccone, K. Browne, M. J. Smyth, and J. A. Trapani Calcium-dependent Plasma Membrane Binding and Cell Lysis by Perforin Are Mediated through Its C2 Domain: A CRITICAL ROLE FOR ASPARTATE RESIDUES 429, 435, 483, AND 485 BUT NOT 491 J. Biol. Chem., March 4, 2005; 280(9): 8426 - 8434. [Abstract] [Full Text] [PDF]

				M. Bots, I. G. M. Kolfschoten, S. A. Bres, M. T. G. A. Rademaker, G. M. de Roo, M. Kruse, K. L. M. C. Franken, M. Hahne, C. J. Froelich, C. J. M. Melief, et al. SPI-CI and SPI-6 cooperate in the protection from effector cell-mediated cytotoxicity Blood, February 1, 2005; 105(3): 1153 - 1161. [Abstract] [Full Text] [PDF]

				S. Mahrus, W. Kisiel, and C. S. Craik Granzyme M Is a Regulatory Protease That Inactivates Proteinase Inhibitor 9, an Endogenous Inhibitor of Granzyme B J. Biol. Chem., December 24, 2004; 279(52): 54275 - 54282. [Abstract] [Full Text] [PDF]

				J. Hanna, P. Bechtel, Y. Zhai, F. Youssef, K. McLachlan, and O. Mandelboim Novel Insights on Human NK Cells' Immunological Modalities Revealed by Gene Expression Profiling J. Immunol., December 1, 2004; 173(11): 6547 - 6563. [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]