REQUIREMENT OF AN ICE/CED-3 PROTEASE FOR FAS/APO-1-MEDIATED APOPTOSIS
REQUIREMENT OF AN ICE/CED-3 PROTEASE FOR FAS/APO-1-MEDIATED APOPTOSIS
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DOI：
10.1038/375081a0
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发表时间：
1995-05-04
期刊：
影响因子：
64.8
通讯作者：
SCHULZEOSTHOFF, K
中科院分区：
文献类型：
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作者：
LOS, M;VANDECRAEN, M;SCHULZEOSTHOFF, K
Fas/APO-1受体是细胞凋亡的主要调控因子之一（1-7）。我们在这里报道Fas/ apo -1介导的细胞凋亡需要激活一类新的半胱氨酸蛋白酶，包括白细胞介素-1 β转换酶（ICE）（8-10），它与线虫细胞死亡基因ced-3的产物同源（参考文献11,12）。Fas/APO-1的触发迅速刺激了ICE的蛋白水解活性。通过电穿孔和显微注射实现的ICE过表达，强烈增强了Fas/ apo -1介导的细胞死亡。此外，蛋白酶抑制剂抑制ICE活性，以及短暂表达痘病毒衍生的丝氨酸蛋白酶抑制剂CrmA或反义ICE构建物，可显著抑制Fas/ apo -1引发的细胞死亡。我们得出结论，ICE或ICE相关蛋白酶的激活是Fas/ apo -1介导的细胞死亡的关键事件。
THE Fas/APO-1 receptor is one of the major regulators of apoptosis(1-7). We report here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-1 beta-converting enzyme (ICE)(8-10) which are homologous to the product of the Caenorhabditis elegans cell-death gene ced-3 (refs 11, 12). Triggering of Fas/APO-1 rapidly stimulated the proteolytic activity of ICE. Overexpression of ICE, achieved by electroporation and microinjection, strongly potentiated Fas/APO-1-mediated cell death. In addition, inhibition of ICE activity by protease inhibitors, as well as by transient expression of the pox virus-derived serpin inhibitor CrmA or an antisense ICE construct, substantially suppressed Fas/APO-1-triggered cell death. We conclude that activation of ICE or an ICE-related protease is a critical event in Fas/APO-1-mediated cell death.