Boldin M P, Goncharov T M, Goltsev Y V, Wallach D
Department of Membrane Research and Biophysics, The Weizmann Institute of Science, Rehovot, Israel.
Cell. 1996 Jun 14;85(6):803-15. doi: 10.1016/s0092-8674(00)81265-9.
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/CED-3 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.
Fas/APO-1和p55肿瘤坏死因子（TNF）受体（p55-R）激活导致细胞死亡的细胞机制。这些受体激活后，Fas/APO-1结合一种名为MORT1（或FADD）的蛋白质，p55-R结合一种名为TRADD的蛋白质。MORT1和TRADD也能相互结合。我们克隆了一种与MORT1结合的新型蛋白质MACH。这种蛋白质以多种异构体形式存在，其中一些含有具有蛋白水解活性的区域，并且与ICE/CED-3家族的蛋白酶具有明显的序列同源性。蛋白水解性MACH异构体的细胞表达会导致细胞死亡。含有不完整ICE/CED-3区域的MACH异构体的表达能有效保护细胞免受Fas/APO-1或p55-R触发诱导的细胞毒性。这些发现表明，MACH是Fas/APO-1和p55-R诱导的细胞死亡信号级联反应中最上游的酶成分。
