INVOLVEMENT OF AN ICE-LIKE PROTEASE IN FAS-MEDIATED APOPTOSIS
INVOLVEMENT OF AN ICE-LIKE PROTEASE IN FAS-MEDIATED APOPTOSIS
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DOI：
10.1038/375078a0
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发表时间：
1995-05-04
期刊：
影响因子：
64.8
通讯作者：
NAGATA, S
中科院分区：
文献类型：
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作者：
ENARI, M;HUG, H;NAGATA, S
FAS是一种I型膜蛋白，可转导凋亡信号（1，2）。Fas配体或激动性抗Fas抗体与Fas的结合通过细胞凋亡杀死细胞（3）。对秀丽隐杆线虫的研究表明，蛋白酶如白细胞介素-1 β转化酶（ICE）或C.线虫细胞死亡基因ced-3参与凋亡信号转导（4）。ICE的活性可被crmA的产物抑制，crmA是牛痘病毒编码的一种病毒应答修饰基因（5-7）。我们在这里报告，crmA的表达抑制抗PAS抗体或肿瘤坏死因子（TNF）诱导的细胞毒性。我们已经发现了一种特异性ICE抑制剂四肽（乙酰基-Tyr-Val-Ala-Asp-氯甲基酮）（8，9），其也可预防抗Fas抗体诱导的细胞凋亡。这些结果表明，一个ICE样蛋白酶参与Fas介导的细胞凋亡和TNF诱导的细胞毒性。
FAS is a type-I membrane protein that transduces an apoptotic signal(1,2). Binding of Fas ligand or agonistic anti-Fas antibody to Fas kills the cells by apoptosis(3). Studies in the nematode Caenorhabditis elegans have suggested that proteases such as interleukin-1 beta-converting enzyme (ICE) or the product of the C. elegans cell-death gene ced-3 are involved in apoptotic signal transduction(4). The activity of ICE can be inhibited by the product of crmA, a cytokine-response modifier gene encoded by cowpox virus(5-7). We report here that expression of crmA inhibits cytotoxicity induced by anti-pas antibody or tumour necrosis factor (TNF). We have found a specific ICE inhibitor tetrapeptide (acetyl-Tyr-Val-Ala-Asp-chloromethylketone)(8,9) that also prevents apoptosis induced by anti-Fas antibody. These results suggest an involvement of an ICE-like protease in Fas-mediated apoptosis and TNF-induced cytotoxicity.