Death Receptor Activation Complexes It Takes Two to Activate TNF Receptor 1
Death Receptor Activation Complexes It Takes Two to Activate TNF Receptor 1
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DOI：
10.4161/cc.2.6.566
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发表时间：
2003-01-01
期刊：
影响因子：
4.3
通讯作者：
Huang, Ying
中科院分区：
文献类型：
--
作者：
Sheikh, M. Saeed;Huang, Ying
细胞凋亡的外在途径起源于膜并与膜死亡受体结合。肿瘤坏死因子受体 1 (TNF-R1) 是一种死亡受体，可转导死亡和生存信号，但 TNF-R1 介导这些信号的分子机制仍知之甚少。最近，据报道TNF-R1通过两个信号复合物转导这些信号。第一个复合物（复合物 I）由 TNF-R1、TRADD、RIP、TRAF2 和 c-IAP1 在膜上形成，而第二个复合物（复合物 II）在细胞质中形成，主要包含 FADD 和前半胱天冬酶 8/10，但缺乏 TNF-R1。复合物 I 负责激活 NF-κ B，从而转导生存信号。另一方面，据报道，复合物 II 可以转导细胞凋亡信号，并且只有当 NF-kappa B 无法促进抗细胞凋亡 FLIPL 上调时，它才会这样做。这些发现强调了 TNF-R1 介导的信号事件的复杂性，可能会进一步推动死亡受体依赖性信号通路不断发展的领域的进展。
The extrinsic pathway of apoptosis originates at the membrane and engages membrane death receptors. Tumor necrosis factor receptor 1 (TNF-R1) is a death receptor that transduces both the death and survival signals but the molecular mechanisms via which TNF-R1 mediates these signals remain poorly understood. Recently, it has been reported that the TNF-R1 transduces these signals via two signaling complexes. The first complex (complex I) is formed at the membrane by TNF-R1, TRADD, RIP, TRAF2 and c-IAP1, while the second complex (complex II), formed in the cytosol, predominantly contains FADD and pro-caspases 8/10 but lacks TNF-R1. Complex I is responsible for activating NF-kappa B and thus, the transduction of survival signals. Complex II, on the other hand, is reported to transduce the apoptotic signals and it does so only if NF-kappa B is unable to promote upregulation of the anti-apoptotic FLIPL. These findings highlighting the complexities of TNF-R1-mediated signaling events are likely to further the progress in the constantly evolving area of death receptor-dependent signaling pathways.