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.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 23 Feb 2001|
Bibliographical noteFunding Information:
This work was supported in part by Molecular Medical Science Research Grant 02-02-A-02 and Center of Excellence Grant 1998G0202. Y. Chung and J. Baek were supported in part by BK21 fellowship from Ministry of Education. We thank Dr. M. Bevan for the pMI retroviral vector; and Dr. H. Nakano for FLAG-tagged IKK-α expression plasmid. We are grateful to J. R. Arron for critical reading of the manuscript.
- Signal transduction