JNK/SAPK activity contributes to TRAIL-induced apoptosis

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 (alpha APO-1) was also diminished by dominant-negative FADD or zVAD. Correspondingly, a cell line resistant to alpha APO-1-induced death exhibited crossresistance to TRAIL-induced apoptosis and did not upregulate JNK/SAPK activity in response to TRAIL or alpha APO-1. Inhibition of JNK/SAPK activity, by stably transfecting cells with a dominant-negative JNKK-MKK4 construct, reduced apoptosis in response to TRAIL or alpha APO-1. Therefore, activation of JNK/SAPKs by TRAIL or alpha APO-1 occurs downstream of FADD and caspases and contributes to apoptosis in human lymphoid cell lines.