Figure 8
CD40-mediated apoptosis in carcinoma cells. Schematic diagram of the signalling pathway that underpins mCD40L-mediated, tumour cell-specific apoptosis. Unlike CD40 engagement by soluble agonist that does not adequately activate the receptor to stabilise TRAF3 and initiate signalling, ligation of CD40 by mCD40L recruits and upregulates TRAF3 and activates p40phox to induce rapid ROS elevation – which appears to be essential for TRAF3 stabilisation. The generated ROS mediates the oxidation and inactivation of Trx (Trx-1), permitting activation of ASK-1 and subsequent phosphorylation of MKK4 and JNK to activate the JNK/AP-1 cascade which is responsible for the induction of Bax and Bak expression. This triggers the intrinsic, cytochrome c-driven, caspase-9 dependent mitochondrial pathway that drives apoptosis.
