Caspase-2 is activated at the CD95 death-inducing signaling complex in the course of CD95-induced apoptosis

被引:50
作者
Lavrik, Inna N. [1 ]
Golks, Alexander [1 ]
Baumann, Simone [1 ]
Krammer, Peter H. [1 ]
机构
[1] German Canc Res Ctr, Div Immunogenet, Tumorimmunol Program, D-69120 Heidelberg, Germany
关键词
D O I
10.1182/blood-2005-07-007096
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Caspase-2 was reported to be involved in a number of apoptotic pathways triggered by various stimuli. However, the molecular mechanism of procaspase-2 activation in the course of apoptosis remains poorly defined. In this report, we demonstrate that procaspase-2 is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex (DISC) in human T- and B-cell lines. We show that procaspase-2 is activated at the DISC on CD95 stimulation. Despite its presence at the DISC, caspase-2 does not initiate apoptosis on CD95 stimulation in caspase-8-deficient cell lines. Taken together, our data reveal that caspase-2 is activated at the DISC but does not play an initiating role in the CD95-induced apoptosis.
引用
收藏
页码:559 / 565
页数:7
相关论文
共 42 条
[1]  
Ahmad M, 1997, CANCER RES, V57, P615
[2]   The domains of death: evolution of the apoptosis machinery [J].
Aravind, L ;
Dixit, VM ;
Koonin, EV .
TRENDS IN BIOCHEMICAL SCIENCES, 1999, 24 (02) :47-53
[3]   The biochemical mechanism of caspase-2 activation [J].
Baliga, BC ;
Read, SH ;
Kumar, S .
CELL DEATH AND DIFFERENTIATION, 2004, 11 (11) :1234-1241
[4]   CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells [J].
Barnhart, BC ;
Legembre, P ;
Pietras, E ;
Bubici, C ;
Franzoso, G ;
Peter, ME .
EMBO JOURNAL, 2004, 23 (15) :3175-3185
[5]   Defects in regulation of apoptosis in caspase-2-deficient mice [J].
Bergeron, L ;
Perez, GI ;
Macdonald, G ;
Shi, LF ;
Sun, Y ;
Jurisicova, A ;
Varmuza, S ;
Latham, KE ;
Flaws, JA ;
Salter, JCM ;
Hara, H ;
Moskowitz, MA ;
Li, E ;
Greenberg, A ;
Tilly, JL ;
Yuan, JY .
GENES & DEVELOPMENT, 1998, 12 (09) :1304-1314
[6]   HOXA5-induced apoptosis in breast cancer cells is mediated by caspases 2 and 8 [J].
Chen, HX ;
Chung, S ;
Sukumar, S .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (02) :924-935
[7]   Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment [J].
Chou, JJ ;
Matsuo, H ;
Duan, H ;
Wagner, G .
CELL, 1998, 94 (02) :171-180
[8]   Involvement of caspase-2 long isoform in Fas-mediated cell death of human leukemic cells [J].
Droin, N ;
Bichat, F ;
Rébé, C ;
Wotawa, A ;
Sordet, O ;
Hammann, A ;
Bertrand, R ;
Solary, E .
BLOOD, 2001, 97 (06) :1835-1844
[9]   RAIDD is a new 'death' adaptor molecule [J].
Duan, H ;
Dixit, VM .
NATURE, 1997, 385 (6611) :86-89
[10]   c-FLIPR, a new regulator of death receptor-induced apoptosis [J].
Golks, A ;
Brenner, D ;
Fritsch, C ;
Krammer, PH ;
Lavrik, IN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (15) :14507-14513