Figure 1. Scheme of the role of Bid for the synergistic interaction of TRAIL and Bortezomib.

TRAIL induces cleavage of Bid into tBid, while Bortezomib increases the stabilization of tBid by inhibiting its proteasomal degradation, resulting in accumulation of tBid at mitochondrial membranes. This in turn promotes activation of Bax/Bak, release of cytochrome c from mitochondria into the cytosol, caspase-3 activation and caspase-dependent apoptosis.