Abstract
We report here that JNK/SAPKs are activated by TRAIL in parallel to induction of apoptosis in human T and B cell lines. Death signaling as well as JNK/SAPK activation by TRAIL in these cells is FADD- and caspase-dependent since dominant-negative FADD or the caspase inhibitor zVAD prevented both, apoptosis and JNK/SAPK activity. JNK/SAPK activity in response to triggering of CD95 by an agonistic antibody (αAPO-1) was also diminished by dominant-negative FADD or zVAD. Correspondingly, a cell line resistant to αAPO-1-induced death exhibited crossresistance to TRAIL-induced apoptosis and did not upregulate JNK/SAPK activity in response to TRAIL or αAPO-1. Inhibition of JNK/SAPK activity, by stably transfecting cells with a dominant-negative JNKK-MKK4 construct, reduced apoptosis in response to TRAIL or αAPO-1. Therefore, activation of JNK/SAPKs by TRAIL or αAPO-1 occurs downstream of FADD and caspases and contributes to apoptosis in human lymphoid cell lines.
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Herr, I., Wilhelm, D., Meyer, E. et al. JNK/SAPK activity contributes to TRAIL-induced apoptosis. Cell Death Differ 6, 130–135 (1999). https://doi.org/10.1038/sj.cdd.4400467
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DOI: https://doi.org/10.1038/sj.cdd.4400467
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