Thornberry N A
Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey, 07065, USA.
Br Med Bull. 1997;53(3):478-90. doi: 10.1093/oxfordjournals.bmb.a011625.
The discovery that CED-3, the product of a gene necessary for programmed cell death in the nematode Caenorhabditis elegans, is related to the mammalian cysteine protease interleukin-1 beta converting enzyme (ICE/caspase-1) has led to intense interest in the role of proteases in apoptosis. It is now clear that at least some members of the caspase (ICE/CED-3) family, which at present includes ten homologues of human origin, are essential components of an evolutionarily conserved pathway of apoptosis. These enzymes appear to be involved in both the initial signaling events and the downstream proteolytic cleavages that result in the apoptotic phenotype. Selective macromolecular and peptide-based inhibitors attenuate apoptosis in whole cells, suggesting that one or more of these enzymes will be suitable targets for therapeutic intervention in diseases resulting from inappropriate cell death.
线虫秀丽隐杆线虫中程序性细胞死亡所必需的一种基因的产物CED-3,与哺乳动物半胱氨酸蛋白酶白细胞介素-1β转换酶(ICE/半胱天冬酶-1)相关,这一发现引发了人们对蛋白酶在细胞凋亡中作用的浓厚兴趣。现在很清楚,半胱天冬酶(ICE/CED-3)家族的至少一些成员(目前包括十种源自人类的同源物)是细胞凋亡进化保守途径的重要组成部分。这些酶似乎既参与初始信号事件,也参与导致凋亡表型的下游蛋白水解切割。选择性的基于大分子和肽的抑制剂可减弱全细胞中的细胞凋亡,这表明这些酶中的一种或多种将成为因细胞死亡不当导致的疾病治疗干预的合适靶点。