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Caspase involvement in RIP-associated CD95-induced T cell apoptosis
Rita N Bárcia1, Nicola S Della Valle, Julie D McLeod
1Centre for Research in Biomedicine, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, UK.
Cellular Immunology
|February 14, 2004
Summary
Receptor-interacting protein (RIP) kinase plays a crucial role in CD95-induced apoptosis in T cells. Its absence or degradation reduces T cell death, confirming RIP
Area of Science:
- Immunology
- Cell Biology
- Molecular Signaling
Background:
- CD95 (Fas receptor) signaling is critical for T cell apoptosis.
- Receptor-interacting protein (RIP) kinase, known for TNF signaling, also possesses a death domain.
- RIP's role in CD95-mediated apoptosis and its interaction with caspases requires elucidation.
Purpose of the Study:
- To investigate the role of RIP in CD95-induced apoptosis in T cells.
- To examine the inter-relationship between RIP and the caspase cascade in this process.
- To confirm RIP cleavage upon CD95 ligand stimulation.
Main Methods:
- Utilized RIP-/- T cell lines and peripheral T lymphocytes.
- Degraded RIP using geldanamycin.
- Induced apoptosis with membrane-bound CD95-Ligand (CD95-L).
- Assessed caspase activity (caspases 2, 8, 9, and 3) and RIP cleavage.
- Investigated the effect of Z-VAD (caspase inhibitor).
Main Results:
- RIP-/- T cells exhibited reduced susceptibility to CD95-induced apoptosis.
- RIP cleavage was observed upon CD95-L stimulation, partially inhibited by Z-VAD.
- Absence of RIP led to decreased activity of initiator and effector caspases.
- RIP-associated apoptosis was confirmed to be caspase-dependent.
Conclusions:
- RIP is essential for efficient CD95-induced apoptosis in T cells.
- RIP cleavage upon CD95-L stimulation suggests a role in the apoptotic pathway.
- RIP functions in a caspase-dependent manner within the CD95 apoptotic signaling cascade.