Reaper-induced apoptosis in a vertebrate system

被引:69
作者
Evans, EK
Kuwana, T
Strum, SL
Smith, JJ
Newmeyer, DD
Kornbluth, S
机构
[1] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
[2] La Jolla Inst Allergy & Immunol, Div Cellular Immunol, San Diego, CA 92121 USA
关键词
apoptosis; reaper; Xenopus;
D O I
10.1093/emboj/16.24.7372
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
The reaper protein of Drosophila melanogaster has been shown to be a central regulator of apoptosis in that organism, However, it has not been shown to function in any vertebrate nor have the cellular components required for its action been defined, In this report we show that reaper can induce rapid apoptosis in vitro using an apoptotic reconstitution system derived from Xenopus eggs, Moreover, we show that a subcellular fraction enriched in mitochondria is required for this process and that reaper, acting in conjunction with cytosolic factors, can trigger mitochondrial cytochrome c release. Bcl-2 antagonizes these effects, but high levels of reaper can overcome the Bcl-2 block, These results demonstrate that reaper can function in a vertebrate contest, suggesting that reaper-responsive factors are conserved elements of the apoptotic program.
引用
收藏
页码:7372 / 7381
页数:10
相关论文
共 32 条
[1]   CELL-DEATH IN HEALTH AND DISEASE - THE BIOLOGY AND REGULATION OF APOPTOSIS [J].
BELLAMY, COC ;
MALCOMSON, RDG ;
HARRISON, DJ ;
WYLLIE, AH .
SEMINARS IN CANCER BIOLOGY, 1995, 6 (01) :3-16
[2]   Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death [J].
Boldin, MP ;
Goncharov, TM ;
Goltsev, YV ;
Wallach, D .
CELL, 1996, 85 (06) :803-815
[3]   INHIBITION OF ICE FAMILY PROTEASES BY BACULOVIRUS ANTIAPOPTOTIC PROTEIN P35 [J].
BUMP, NJ ;
HACKETT, M ;
HUGUNIN, M ;
SESHAGIRI, S ;
BRADY, K ;
CHEN, P ;
FERENZ, C ;
FRANKLIN, S ;
GHAYUR, T ;
LI, P ;
LICARI, P ;
MANKOVICH, J ;
SHI, LF ;
GREENBERG, AH ;
MILLER, LK ;
WONG, WW .
SCIENCE, 1995, 269 (5232) :1885-1888
[4]   Apoptotic activity of REAPER is distinct from signaling by the tumor necrosis factor receptor 1 death domain [J].
Chen, P ;
Lee, P ;
Otto, L ;
Abrams, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (42) :25735-25737
[5]   FADD, A NOVEL DEATH DOMAIN-CONTAINING PROTEIN, INTERACTS WITH THE DEATH DOMAIN OF FAS AND INITIATES APOPTOSIS [J].
CHINNAIYAN, AM ;
OROURKE, K ;
TEWARI, M ;
DIXIT, VM .
CELL, 1995, 81 (04) :505-512
[6]  
Chinnaiyan AM, 1996, CURR BIOL, V6, P555
[7]   Interaction of CED-4 with CED-3 and CED-9: A molecular framework for cell death [J].
Chinnaiyan, AM ;
ORourke, K ;
Lane, BR ;
Dixit, VM .
SCIENCE, 1997, 275 (5303) :1122-1126
[8]   RAIDD is a new 'death' adaptor molecule [J].
Duan, H ;
Dixit, VM .
NATURE, 1997, 385 (6611) :86-89
[9]   ICE-LAP3, a novel mammalian homologue of the Caenorhabditis elegans cell death protein ced-3 is activated during fas- and tumor necrosis factor-induced apoptosis [J].
Duan, HJ ;
Chinnaiyan, AM ;
Hudson, PL ;
Wing, JP ;
He, WW ;
Dixit, VM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (03) :1621-1625
[10]   Crk is required for apoptosis in Xenopus egg extracts [J].
Evans, EK ;
Lu, W ;
Strum, SL ;
Mayer, BJ ;
Kornbluth, S .
EMBO JOURNAL, 1997, 16 (02) :230-241