Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death.

Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic pathways. Previous studies have suggested that TNF receptor-associated factor (TRAF) 2 can mediate crucial antiapoptotic signals during TNF stimulation. However, it is unclear how the antiapoptotic signals ...
via TRAF2 in TNF-R1 signaling is regulated. Here we show that TRAF1 is cleaved by caspase-8 into two fragments during apoptosis induced by TNF. Overexpression of the C-terminal cleavage product, TRAF1-c, increased TNF-induced cell death of hybridoma T cells. Importantly, we demonstrate that the cleavage product of TRAF1 coimmunoprecipitates with TRAF2 that is released from the TNF-R1 complex in response to prolonged TNF treatment. These results indicate that caspase-dependent cleavage of TRAF1 generates TRAF1-c fragments that are able to bind TRAF2, and then sequester TRAF2 from the TNF-R1 complex, rendering cells, at least in part, sensitive to TNF.
Mesh Terms:
Animals, Apoptosis, Binding Sites, Caspases, Cell Death, Cell Line, DNA, Recombinant, Dose-Response Relationship, Drug, Humans, Plasmids, Protein Binding, Proteins, Receptors, Tumor Necrosis Factor, Signal Transduction, T-Lymphocytes, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, Tumor Necrosis Factor-alpha
Biochem. Biophys. Res. Commun.
Date: Feb. 23, 2001
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