Kischkel F C, Lawrence D A, Chuntharapai A, Schow P, Kim K J, Ashkenazi A
Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
Immunity. 2000 Jun;12(6):611-20. doi: 10.1016/s1074-7613(00)80212-5.
Fas (APO-1/CD95) and tumor necrosis factor receptor 1 (TNFR1) trigger apoptosis by recruiting the apoptosis initiator caspase-8 through the adaptor FADD. Fas binds FADD directly, whereas TNFR1 binds FADD indirectly, through TRADD. TRADD alternatively recruits the NF-kappaB-inducing adaptor RIP. The TNF homolog Apo2L/TRAIL triggers apoptosis through two distinct death receptors, DR4 and DR5; however, receptor over-expression studies have yielded conflicting results on the ligand's signaling mechanism. Apo2L/TRAIL induced homomeric and heteromeric complexes of DR4 and DR5 and stimulated recruitment of FADD and caspase-8 and caspase-8 activation in nontransfected cells. TRADD and RIP, which bound TNFR1, did not bind DR4 and DR5. Thus, Apo2L/TRAIL and FasL initiate apoptosis through similar mechanisms, and FADD may be a universal adaptor for death receptors.
Fas（APO-1/CD95）和肿瘤坏死因子受体1（TNFR1）通过衔接蛋白FADD募集凋亡起始半胱天冬酶-8来触发细胞凋亡。Fas直接结合FADD，而TNFR1则通过TRADD间接结合FADD。TRADD可选择性地募集诱导核因子κB的衔接蛋白RIP。肿瘤坏死因子同源物Apo2L/TRAIL通过两种不同的死亡受体DR4和DR5触发细胞凋亡；然而，受体过表达研究在配体的信号传导机制上得出了相互矛盾的结果。Apo2L/TRAIL诱导DR4和DR5的同源和异源复合物形成，并在未转染的细胞中刺激FADD和半胱天冬酶-8的募集以及半胱天冬酶-8的激活。与TNFR1结合的TRADD和RIP不与DR4和DR5结合。因此，Apo2L/TRAIL和FasL通过相似的机制启动细胞凋亡，并且FADD可能是死亡受体的通用衔接蛋白。
