TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways
TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways
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DOI：
10.1016/s0092-8674(00)80984-8
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发表时间：
1996-01-26
期刊：
影响因子：
64.5
通讯作者：
Goeddel, DV
中科院分区：
文献类型：
--
作者：
Hsu, HL;Shu, HB;Goeddel, DV
肿瘤坏死因子（TNF）可通过TNF受体1（TNFR 1）发出的信号级联反应诱导细胞凋亡并激活NF-κ B B。TRADD是一种TNFR 1相关的信号转导物，参与激活这两种途径。在这里，我们表明TRADD直接与TRAF 2和FADD相互作用，分别激活NF-κ B和诱导凋亡的信号转导。TRAF 2突变体缺乏其N-末端RING指结构域，是TNF介导的NF-κ B激活的显性负性抑制剂，但不影响TNF诱导的细胞凋亡。相反，缺乏其N-末端79个氨基酸的FADD突变体是TNF诱导的细胞凋亡的显性负性抑制剂，但不抑制NF-κ B活化。因此，这两个TNFR 1-TRADD信号级联似乎在TRADD处分叉。
Tumor necrosis factor (TNF) can induce apoptosis and activate NF-kappa B through signaling cascades emanating from TNF receptor 1 (TNFR1). TRADD is a TNFR1-associated signal transducer that is involved in activating both pathways. Here we show that TRADD directly interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce apoptosis, respectively. A TRAF2 mutant lacking its N-terminal RING finger domain is a dominant-negative inhibitor of TNF-mediated NF-kappa B activation, but does not affect TNF-induced apoptosis. Conversely, a FADD mutant lacking its N-terminal 79 amino acids is a dominant-negative inhibitor of TNF-induced apoptosis, but does not inhibit NF-kappa B activation. Thus, these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD.