Figure 6
A model for cell death signalling pathways induced by SW III-123. SW III-123 is internalised cells through sigma-2 receptor (σ2R)-mediated endocytosis. SW III-123 degrades cIAP1 and cIAP2, and thus antagonises cIAP1/2-mediated NF-κB-inducing kinase (NIK) degradation, induces nuclear factor (NF)-κB activation and subsequent tumour necrosis factor alpha (TNFα) production. TNFα binds to TNFR and induces extrinsic and intrinsic apoptotic pathways, leading to caspase-8, -9 and -3 activation. SW III-123 also binds to XIAP, and thus removes the inhibition of XIAP to caspase-9, promoting apoptosis. IAP, inhibitor of apoptosis protein.
