Shu H B, Takeuchi M, Goeddel D V
Tularik, Inc., South San Francisco, CA 94080, USA.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13973-8. doi: 10.1073/pnas.93.24.13973.
The two cell surface receptors for tumor necrosis factor (TNF) interact with a number of intracellular signal transducing proteins. The association of TRADD, a 34-kDa cytoplasmic protein containing a C-terminal death domain, with aggregated TNF receptor 1 (TNF-R1) through their respective death domains leads to NF-kappa B activation and programmed cell death. In contrast, TNF receptor 2 (TNF-R2) interacts with the TNF receptor associated factors 2/1 (TRAF2/TRAF1) heterocomplex, which mediates the recruitment of two cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) to TNF-R2. Here we show that the TNF-R2 signal transducers TRAF2 and c-IAP1 are a part of the TNF-R1 signaling complex. The recruitment of TRAF2 and c-IAP1 to TNF-R1 is TNF-dependent, is mediated by TRADD, and is independent of TNF-R2. These data establish the physiological involvement of TRAF2 and c-IAP1 in TNF-R1 signaling and help provide a molecular explanation for both the overlapping and distinct signals generated by the two TNF receptors.
肿瘤坏死因子（TNF）的两种细胞表面受体与多种细胞内信号转导蛋白相互作用。TRADD是一种34 kDa的细胞质蛋白，含有一个C末端死亡结构域，它通过各自的死亡结构域与聚集的肿瘤坏死因子受体1（TNF-R1）结合，导致核因子κB激活和程序性细胞死亡。相比之下，肿瘤坏死因子受体2（TNF-R2）与肿瘤坏死因子受体相关因子2/1（TRAF2/TRAF1）异源复合物相互作用，该复合物介导两种细胞凋亡抑制蛋白（c-IAP1和c-IAP2）募集到TNF-R2。在这里，我们表明TNF-R2信号转导分子TRAF2和c-IAP1是TNF-R1信号复合物的一部分。TRAF2和c-IAP1募集到TNF-R1是TNF依赖性的，由TRADD介导，且不依赖于TNF-R2。这些数据证实了TRAF2和c-IAP1在TNF-R1信号传导中的生理作用，并有助于为两种TNF受体产生的重叠和不同信号提供分子解释。
