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Transducing signals of life and death
1Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Abstract:
The molecules that form signaling complexes with the cytoplasmic domains of tumor necrosis factor (TNF) receptors (TNF-Rs) and CD95 have been identified recently. The death-signaling pathways induced by TNF-R1 and CD95 involve a group of death domain containing proteins, including caspase-8, a member of the interleukin-1beta-converting enzyme family. TNF-R1 and TNF-R2 also interact with the members of both the TNF-R associated factor family and the inhibitor of apoptosis protein family; these interactions lead to cell survival.
Insights
Tumor necrosis factor (TNF) receptor and CD95 signaling pathways involve death domain proteins like caspase-8 for cell death. Interactions with TNF-R associated factors and inhibitor of apoptosis proteins promote cell survival.
Area of Science:
- Molecular Biology
- Cell Signaling
- Immunology
Background:
- Recent identification of molecules forming signaling complexes with tumor necrosis factor (TNF) receptors (TNF-Rs) and CD95.
- Understanding the molecular mechanisms of TNF-R1 and CD95 mediated signaling is crucial for cell fate determination.
Purpose of the Study:
- To elucidate the molecular players involved in TNF-R and CD95 signaling pathways.
- To differentiate between pathways leading to cell death and cell survival.
Main Methods:
- Identification of signaling complex components.
- Analysis of protein-protein interactions within TNF receptor pathways.
Main Results:
- Caspase-8, an interleukin-1beta-converting enzyme family member, is involved in TNF-R1 and CD95 induced death signaling.
- TNF-R1 and TNF-R2 interact with TNF-R associated factors and inhibitor of apoptosis proteins, mediating cell survival signals.
Conclusions:
- TNF receptor and CD95 signaling pathways utilize distinct molecular complexes to regulate cell death and survival.
- Caspase-8 is a key mediator of apoptosis in response to TNF-R1 and CD95 activation.