Hasegawa J, Kamada S, Kamiike W, Shimizu S, Imazu T, Matsuda H, Tsujimoto Y
First Department of Surgery, Osaka University Medical School, Japan.
Cancer Res. 1996 Apr 15;56(8):1713-8.
Fas (Apo-1/CD95) belongs to the tumor necrosis factor/nerve growth factor receptor family and transmits apoptotic signals by binding to its ligand. Interleukin-1beta-converting enzyme (ICE), which shows substantial homology to the product of the cell death gene, ced-3, of Caenorhabditis elegans, is reported to be involved in Fas-mediated apoptosis. Using two human carcinoma-derived cell lines with undetectable levels of ICE, we found that an agonistic antihuman Fas antibody induces the activation of CPP32/Yama(-like) proteases that are ICE(-like) protease family members, and that a tetrapeptide inhibitor of CPP32/Yama protease, DEVD-CHO, inhibits the Fas-mediated activation of the proteases, Fas-mediated apoptosis, and CPP32/Yama(-like) proteolytic activities in vitro. Fas-mediated apoptosis is inhibited by the CPP32/Yama inhibitor DEVD-CHO, but not by the ICE inhibitor YVAD-CHO, suggesting a dominant role for the CPP32/Yama(-like) proteases and not ICE itself in Fas-mediated apoptosis of the human carcinoma cell lines.
Fas（Apo -1/CD95）属于肿瘤坏死因子/神经生长因子受体家族，通过与配体结合传递凋亡信号。白细胞介素 -1β转化酶（ICE）与秀丽隐杆线虫细胞死亡基因ced -3的产物具有高度同源性，据报道其参与Fas介导的凋亡过程。利用两种人源癌细胞系，其ICE水平检测不到，我们发现一种激动性抗人Fas抗体可诱导CPP32/Yama（类）蛋白酶激活，这些蛋白酶是ICE（类）蛋白酶家族成员，并且一种CPP32/Yama蛋白酶的四肽抑制剂DEVD - CHO可在体外抑制Fas介导的蛋白酶激活、Fas介导的凋亡以及CPP32/Yama（类）蛋白水解活性。Fas介导的凋亡受到CPP32/Yama抑制剂DEVD - CHO的抑制，但不受ICE抑制剂YVAD - CHO的抑制，这表明在人癌细胞系的Fas介导的凋亡中，CPP32/Yama（类）蛋白酶而非ICE本身起主导作用。
