Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death
Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death
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DOI：
10.1016/s0092-8674(00)81265-9
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发表时间：
1996-06-14
期刊：
影响因子：
64.5
通讯作者：
Wallach, D
中科院分区：
文献类型：
--
作者：
Boldin, MP;Goncharov, TM;Wallach, D
Fas/APO-1和P55肿瘤坏死因子受体(P55-R)激活导致细胞死亡的细胞机制。当这些受体被激活时，Fas/APO-1与一种名为MORT1(或FADD)的蛋白质结合，而P55-R与一种名为Tradd的蛋白质结合。MORT1和Tradd也可以相互绑定。我们克隆了一种新的与MORT1结合的蛋白质Mach。该蛋白以多种异构体存在，其中一些含有一个具有蛋白分解活性的区域，并显示出与ICE/CED-3家族的蛋白酶显著的序列同源性。蛋白水解型马赫异构体的细胞表达导致细胞死亡。表达含有不完整ICE/CEDE区域的MACH亚型可有效对抗Fas/APO-1或P55-R触发的细胞毒作用。这些发现表明，在Fas/APO-1和P55-R诱导的细胞死亡信号级联中，Mach是最上游的酶组分。
Fas/APO-1 and p55 tumor necrosis factor (TNF) receptor (p55-R) activate cellular mechanisms that result in cell death. Upon activation of these receptors, Fas/APO-1 binds a protein called MORT1 (or FADD) and p55-R binds a protein called TRADD. MORT1 and TRADD can also bind to each other. We have cloned a novel protein, MACH, that binds to MORT1. This protein exists in multiple isoforms, some of which contain a region that has proteolytic activity and shows marked sequence homology to proteases of the ICE/CED-3 family. Cellular expression of the proteolytic MACH isoforms results in cell death. Expression of MACH isoforms that contain an incomplete ICE/CEDE region provides effective protection against the cytotoxicity induced by Fas/APO-1 or p55-R triggering. These findings suggest that MACH is the most upstream enzymatic component in the Fas/APO-1- and p55-R-induced cell death signaling cascades.