TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways.
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.
Pubmed ID: 8565075 RIS Download
Adaptor Proteins, Signal Transducing | Amino Acid Sequence | Animals | Antigens, CD | Apoptosis | Carrier Proteins | Cell Line | Fas-Associated Death Domain Protein | Humans | Interleukin-1 | Mice | Molecular Sequence Data | NF-kappa B | Proteins | Receptors, Tumor Necrosis Factor | Receptors, Tumor Necrosis Factor, Type I | Sequence Deletion | Signal Transduction | TNF Receptor-Associated Death Domain Protein | TNF Receptor-Associated Factor 1 | TNF Receptor-Associated Factor 2 | Transcriptional Activation | Tumor Necrosis Factor Receptor-Associated Peptides and Proteins | Tumor Necrosis Factor-alpha