Granzyme H induces apoptosis of target tumor cells characterized by DNA fragmentation and Bid-dependent mitochondrial damage

被引：61

作者：

Hou, Qiang ^{[1
]}

Zhao, Tongbiao ^{[1
]}

Zhang, Honglian ^{[1
]}

Lu, Hongxia ^{[1
]}

Zhang, Qixiang ^{[1
]}

Sun, Lei ^{[2
]}

Fan, Zusen ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, Ctr Infect & Immun, Natl Lab Biomacromol, Beijing 100101, Peoples R China

[2] Chinese Acad Sci, Inst Biophys, Ctr Biol Electron Microscopy, Natl Lab Biomacromol, Beijing 100101, Peoples R China

来源：

MOLECULAR IMMUNOLOGY | 2008年 / 45卷 / 04期

基金：

中国国家自然科学基金;

关键词：

granzyme H; apoptosis; caspase; bid; mitochondrial damage;

D O I：

10.1016/j.molimm.2007.07.032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Natural killer (NK) cells are the effectors of innate immunity to act as the first line of defense against viruses and tumors. Granzyme H (GzmH) is predicted to evolve from GzmB and constitutively expressed at a high level in human NK cells. It indicates GzmH plays a pivotal role in NK cell mediated cytolysis. However GzmH is defined as an orphan granzyme and its function has less been defined. Here we demonstrate GzmH can induce rapid apoptosis of target cells, which is dependent on caspase activation and mitochondrial damage. GzmH-induced death is characterized by phophatidylserine externalization. nuclear condensation. DNA fragmentation, caspase activation and cytochrome c release that are hallmarks of typical apoptosis. GzmH can directly cleave ICAD to unleash CAD for DNA fragmentation. Moreover, GzmH directly processes Bid to produce the active form tBid leading to cytochrome c release. Therefore, GzmH may play an essential role in caspase-dependent pathogen clearance in the innate immunity that may complement the proapoptotic function of GzmB in human NK cells. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：1044 / 1055

页数：12

共 49 条

[1] Molecular ordering of the caspase activation cascade initiated by the cytotoxic T lymphocyte/natural killer (CTL/NK) protease granzyme B [J].

Adrain, C ;

Murphy, BM ;

Martin, SJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (06) :4663-4673

[2] Granzyme H destroys the function of critical adenoviral proteins required for viral DNA replication and granzyme B inhibition [J].

Andrade, Felipe ;

Fellows, Edward ;

Jenne, Dieter E. ;

Rosen, Antony ;

Young, C. S. H. .

EMBO JOURNAL, 2007, 26 (08) :2148-2157

[3] Cell death: Critical control points [J].

Danial, NN ;

Korsmeyer, SJ .

CELL, 2004, 116 (02) :205-219

[4] ACTIVATION OF THE APOPTOTIC PROTEASE CPP32 BY CYTOTOXIC T-CELL-DERIVED GRANZYME-B [J].

DARMON, AJ ;

NICHOLSON, DW ;

BLEACKLEY, RC .

NATURE, 1995, 377 (6548) :446-448

[5] HIGH-ACTIVITY OF N-ALPHA-BENZYLOXYCARBONYL-L-LYSINE THIOBENZYL ESTER SERINE ESTERASE AND CYTOLYTIC PERFORIN IN CLONED CELL-LINES IS NOT DEMONSTRABLE IN INVIVO-INDUCED CYTOTOXIC EFFECTOR-CELLS [J].

DENNERT, G ;

ANDERSON, CG ;

PROCHAZKA, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (14) :5004-5008

[6] Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition [J].

Du, CY ;

Fang, M ;

Li, YC ;

Li, L ;

Wang, XD .

CELL, 2000, 102 (01) :33-42

[7] The human cytotoxic T cell granule serine protease granzyme H has chymotrypsin-like (chymase) activity and is taken up into cytoplasmic vesicles reminiscent of granzyme B-containing endosomes [J].

Edwards, HM ;

Kam, CM ;

Powers, JC ;

Trapani, JA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (43) :30468-30473

[8] A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD [J].

Enari, M ;

Sakahira, H ;

Yokoyama, H ;

Okawa, K ;

Iwamatsu, A ;

Nagata, S .

NATURE, 1998, 391 (6662) :43-50

[9] Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor [J].

Fan, ZS ;

Beresford, PJ ;

Oh, DY ;

Zhang, D ;

Lieberman, J .

CELL, 2003, 112 (05) :659-672

[10] NK-cell activation by LIGHT triggers tumor-specific CD8+ T-cell immunity to reject established tumors [J].

Fan, ZS ;

Yu, P ;

Wang, Y ;

Wang, YG ;

Fu, ML ;

Liu, WH ;

Sun, YL ;

Fu, YX .

BLOOD, 2006, 107 (04) :1342-1351

← 1 2 3 4 5 →