Los M, Van de Craen M, Penning L C, Schenk H, Westendorp M, Baeuerle P A, Dröge W, Krammer P H, Fiers W, Schulze-Osthoff K
Division of Immunochemistry, German Cancer Research Center, Heidelberg.
Nature. 1995 May 4;375(6526):81-3. doi: 10.1038/375081a0.
The Fas/APO-1 receptor is one of the major regulators of apoptosis. 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), 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.
Fas/APO-1受体是细胞凋亡的主要调节因子之一。我们在此报告，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-1β转换酶（ICE），它们与秀丽隐杆线虫细胞死亡基因ced-3的产物同源（参考文献11、12）。Fas/APO-1的激活迅速刺激了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，蛋白酶抑制剂以及痘病毒衍生的丝氨酸蛋白酶抑制剂CrmA或反义ICE构建体的瞬时表达对ICE活性的抑制，显著抑制了Fas/APO-1触发的细胞死亡。我们得出结论，ICE或与ICE相关的蛋白酶的激活是Fas/APO-1介导的细胞死亡中的关键事件。
