Figure 3

Apoptosis Signalling network. The extrinsic apoptosis pathway is activated upon ligand binding to death receptors (TNFR1, Fas/CD95, DR4/5). This results in activation of a caspase cascade and eventually cleavage of both cytoplasmic and nuclear substrates. TNFR1 may promote survival signalling through activation of NFκB. The intrinsic pathway involves release of apoptotic proteins from the mitochondria, formation of the apoptosome and subsequently caspase activation. Members of the BCL-2 protein family are involved in regulation of the intrinsic apoptotic pathway. The extrinsic and the intrinsic pathways converge in a caspase cascade that results in cellular shrinkage, DNA fragmentation and eventually apoptosis. These pathways are highly deregulated in GBMs. Tumour necrosis factor receptor (TNFR), Tumour necrosis related apoptosis-inducing ligand (TRAIL), TNFR type 1-associated death domain protein (TRADD), Death receptor (DR), Fas-associated protein with death domain (FADD), TNFR associated factor (TRAF), Receptor interacting protein (RIP), FLICE-like inhibitory protein (FLIP), X-linked inhibitor of apoptosis protein (XIAP), Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), Inhibitor of κB (IκB), IκB kinases (IKKs), cytochrome c (Cyt c), Apoptotic protease activating factor 1 (Apaf-1).