Death Receptor Activation Complexes: It Takes Two to Activate TNF Receptor 1

• Published in: Cell cycle (Georgetown, Tex.) Vol. 2; no. 6; pp. 549 - 551
• Main Authors: Sheikh, M. Saeed, Huang, Ying
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-11-2003
• Subjects: Antigens, CD - metabolism; Apoptosis - physiology; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cycle; Humans; Landes; Macromolecular Substances; NF-kappa B - metabolism; Organogenesis; Proteins; Proteins - metabolism; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor, Type I; Signal Transduction - physiology; TNF Receptor-Associated Factor 1
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.2.6.566

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-kB 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-kB 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.