Induction of TNF Receptor I-Mediated Apoptosis via Two Sequential Signaling Complexes

  title={Induction of TNF Receptor I-Mediated Apoptosis via Two Sequential Signaling Complexes},
  author={Olivier Micheau and Jürg Tschopp},

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Death Receptor Activation Complexes: It Takes Two to Activate TNF Receptor 1
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.
Distinct Signaling Pathways in TRAIL- versus Tumor Necrosis Factor-Induced Apoptosis
The data suggest that TNF triggers apoptosis in a manner distinct from that of Fas-L or TRAIL, and Interestingly, TRADD is dispensable, while RIP is required for TNF-induced apoptose in human tumor cells.
Competitive Control of Independent Programs of Tumor Necrosis Factor Receptor-Induced Cell Death by TRADD and RIP1
TNFR1-initiated intracellular signals diverge at a very proximal level by the independent association of two death domain-containing proteins, RIP1 and TRADD, which determine cell fate by triggering NF-κB activation, apoptosis, and nonapoptotic death signals through separate and competing signaling pathways.
TWEAK Induces Apoptosis through a Death-signaling Complex Comprising Receptor-interacting Protein 1 (RIP1), Fas-associated Death Domain (FADD), and Caspase-8
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TNFα induces survival through the FLIP-L-dependent activation of the MAPK/ERK pathway
A previously undescribed and essential role for MAPK/ERK activation by FLIP-L in the decision between cell survival and apoptosis upon TNFα stimulation is reported.
Compartmentalization of TNF-receptor 1 signaling: TNF-R1-associated caspase-8 mediates activation of acid sphingomyelinase in late endosomes.
The fusion of internalized TNF-receptosomes with trans-Golgi vesicles containing the proform of A-SMase should be recognized as a novel mechanism to transduce death signals along the endocytic route.
Molecular Determinants of Kinase Pathway Activation by Apo2 Ligand/Tumor Necrosis Factor-related Apoptosis-inducing Ligand*
It is shown that Apo2L/TRAIL activates kinase pathways by promoting the association of a secondary signaling complex, subsequent to assembly of a primary, death-inducing signaling complex (DISC), which recruited several factors involved in kinase activation by TNF.
TRAF2 Phosphorylation Modulates Tumor Necrosis Factor Alpha-Induced Gene Expression and Cell Resistance to Apoptosis
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NF-κB Signals Induce the Expression of c-FLIP
It is shown that NF-κB activation upregulates the caspase 8 inhibitor FLIP, resulting in increased resistance to Fas ligand (FasL) or TNF, and suggest that FLIP is an important mediator of NF-σκB-controlled antiapoptotic signals.
TNF-Induced Signaling in Apoptosis
Out of the almost 17 members of the TNF superfamily, TNF is probably the most potent inducer of apoptosis. TNF activates both cell-survival and cell-death mechanisms simultaneously. Activation of
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F Fas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic morphological changes and late mitochondrial damage but no cytochrome c release.
Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms
Data indicate that nucleocytoplasmic shuttling of TRADD leads to the activation of distinct apoptosis mechanisms that connect the death receptor apparatus to nuclear events.
Signal transduction by tumor necrosis factor and its relatives.
NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation.
Tumor necrosis factor alpha (TNF-alpha) binding to the TNF receptor (TNFR) potentially initiates apoptosis and activates the transcription factor nuclear factor kappa B (NF-kappaB), which suppresses
Tumor necrosis factor receptor and Fas signaling mechanisms.
The molecules that initiate these signaling events, including the death domain- and TNF receptor associated factor (TRAF) domain-containing adapter proteins and the signaling enzymes associated with them, are largely unique to the TNF/nerve growth factor receptor family.
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The characterization of an inhibitor of apoptosis is reported, designated FLIP (for FLICE-inhibitory protein), which is predominantly expressed in muscle and lymphoid tissues and may be implicated in tissue homeostasis as an important regulator of apoptotic regulation.