Yeh W C, de la Pompa J L, McCurrach M E, Shu H B, Elia A J, Shahinian A, Ng M, Wakeham A, Khoo W, Mitchell K, El-Deiry W S, Lowe S W, Goeddel D V, Mak T W
Amgen Institute, University of Toronto, Toronto, Ontario, Canada.
Science. 1998 Mar 20;279(5358):1954-8. doi: 10.1126/science.279.5358.1954.
FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 (also called Fas). CD95, tumor necrosis factor receptor type 1 (TNFR-1), and death receptor 3 (DR3) did not induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A and c-myc, and chemotherapeutic agent adriamycin did. Mice with a deletion in the FADD gene did not survive beyond day 11.5 of embryogenesis; these mice showed signs of cardiac failure and abdominal hemorrhage. Chimeric embryos showing a high contribution of FADD null mutant cells to the heart reproduce the phenotype of FADD-deficient mutants. Thus, not only death receptors, but also receptors that couple to developmental programs, may use FADD for signaling.
FADD(也称为Mort-1)是细胞死亡受体CD95(也称为Fas)下游的信号转导分子。CD95、肿瘤坏死因子受体1型(TNFR-1)和死亡受体3(DR3)在FADD缺陷的胚胎成纤维细胞中不会诱导细胞凋亡,而DR4、癌基因E1A和c-myc以及化疗药物阿霉素则会。FADD基因缺失的小鼠在胚胎发育第11.5天之后无法存活;这些小鼠表现出心力衰竭和腹腔出血的迹象。嵌合胚胎中FADD基因敲除突变细胞对心脏有高度贡献,重现了FADD缺陷突变体的表型。因此,不仅死亡受体,而且与发育程序偶联的受体,都可能利用FADD进行信号传导。