IDENTIFICATION AND INHIBITION OF THE ICE/CED-3 PROTEASE NECESSARY FOR MAMMALIAN APOPTOSIS

被引:3785
作者
NICHOLSON, DW
ALI, A
THORNBERRY, NA
VAILLANCOURT, JP
DING, CK
GALLANT, M
GAREAU, Y
GRIFFIN, PR
LABELLE, M
LAZEBNIK, YA
MUNDAY, NA
RAJU, SM
SMULSON, ME
YAMIN, TT
YU, VL
MILLER, DK
机构
[1] MERCK FROSST CANADA INC,MERCK FROSST CTR THERAPEUT RES,DEPT MED CHEM,POINTE CLAIRE,PQ H9R 4P8,CANADA
[2] MERCK & CO INC,RES LABS,DEPT BIOCHEM,RAHWAY,NJ 07065
[3] MERCK & CO INC,RES LABS,DEPT INFLAMMAT RES,RAHWAY,NJ 07065
[4] COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724
[5] GEORGETOWN UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC
关键词
D O I
10.1038/376037a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The protease responsible for the cleavage of poly(ADP-ribose) polymerase and necessary for apoptosis has been purified and characterized. This enzyme, named apopain, is composed of two subunits of relative molecular mass (M(r)) 17K and 12K that are derived from a common proenzyme identified as CPP32. This proenzyme is related to interleukin-1 beta-converting enzyme (ICE) and CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans. A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events In vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death.
引用
收藏
页码:37 / 43
页数:7
相关论文
共 48 条
[1]  
AYALA JM, 1994, J IMMUNOL, V153, P2592
[2]  
BARR PJ, 1994, BIO-TECHNOL, V12, P487, DOI 10.1038/nbt0594-487
[3]   DEFECTIVE POLY(ADENOSINE DIPHOSPHORIBOSE) SYNTHESIS IN XERODERMA PIGMENTOSUM [J].
BERGER, NA ;
SIKORSKI, GW ;
PETZOLD, SJ ;
KUROHARA, KK .
BIOCHEMISTRY, 1980, 19 (02) :289-293
[4]  
BURKLE A, 1992, EXP CLIN IMMUNOGENET, V9, P230
[5]  
CARSON DA, 1994, LANCET, V341, P1251
[6]   MOLECULAR-CLONING OF THE INTERLEUKIN-1-BETA CONVERTING ENZYME [J].
CERRETTI, DP ;
KOZLOSKY, CJ ;
MOSLEY, B ;
NELSON, N ;
VANNESS, K ;
GREENSTREET, TA ;
MARCH, CJ ;
KRONHEIM, SR ;
DRUCK, T ;
CANNIZZARO, LA ;
HUEBNER, K ;
BLACK, RA .
SCIENCE, 1992, 256 (5053) :97-100
[7]   SYNTHESIS OF A POTENT, REVERSIBLE INHIBITOR OF INTERLEUKIN-1-BETA CONVERTING ENZYME [J].
CHAPMAN, KT .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1992, 2 (06) :613-618
[8]   CDNA SEQUENCE, PROTEIN-STRUCTURE, AND CHROMOSOMAL LOCATION OF THE HUMAN-GENE FOR POLY(ADP-RIBOSE) POLYMERASE [J].
CHERNEY, BW ;
MCBRIDE, OW ;
CHEN, D ;
ALKHATIB, H ;
BHATIA, K ;
HENSLEY, P ;
SMULSON, ME .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) :8370-8374
[9]   POLY(ADP-RIBOSE) POLYMERASE - MOLECULAR BIOLOGICAL ASPECTS [J].
DEMURCIA, G ;
MENISSIERDEMURCIA, J ;
SCHREIBER, V .
BIOESSAYS, 1991, 13 (09) :455-462
[10]   A COMPREHENSIVE SET OF SEQUENCE-ANALYSIS PROGRAMS FOR THE VAX [J].
DEVEREUX, J ;
HAEBERLI, P ;
SMITHIES, O .
NUCLEIC ACIDS RESEARCH, 1984, 12 (01) :387-395