Figure 4 | Cell Death & Differentiation

Figure 4

From: Apoptosome: a platform for the activation of initiator caspases

Figure 4

Models of initiator caspase activation. (a) Induced-proximity model.8 The induced proximity model states that the initiator caspases auto-process themselves when brought into close proximity of each other.8 The primary supporting evidence was obtained using a fusion protein between the target caspases and a heterologous dimerization domain, such as tandem FKBPs shown here. Binding to the dimeric ligand FK1012 brings together the tethered caspases, resulting in their activation. (b) Proximity-driven dimerization model.73 This model states that dimer formation drives the activation of initiator caspases and the adaptor protein complexes serve to promote dimerization by increasing the local concentrations of initiator caspases. (c) Induced conformation model.12, 80 This model states that the activated conformation of the active site for a given initiator caspase is the ultimate reason for its activation and is attained through direct interaction with the adaptor protein complex or through homo-oligomerization facilitated by the adaptor protein complex. Three scenarios are depicted here. One scenario is that caspase-9 is activated as a monomer, with its active site conformation stabilized directly by the apoptosome. The second scenario is that caspase-9 is activated as a homo-dimer, as proposed by the proximity-driven dimerization model,73 with its active site conformation stabilized by dimer formation and dimer interactions with the apoptosome. The third scenario is that caspase-9 is activated as a higher-order homo-oligomer, with its active site conformation stabilized both by the oligomer and the apoptosome

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