- 期刊
Activation of Initiator Caspases: History, Hypotheses, and Perspectives
並列摘要
Apoptosis is executed by a cascade of caspase activation. Activation of an effector caspase is mediated by specific initiator caspases through an intra-chain cleavage. Activation of an initiator caspase, such as caspase-9, relies on a specific adaptor protein complex, such as apoptosome. Although conclusive mechanisms by which the initiator caspases are activated remain elusive, important insights have emerged from recent investigations. The induced proximity model summarizes the general process of initiator caspase activation. The proximity-driven dimerization model describes how initiator caspases respond to induced proximity and offers an explanation for their activation. However caspases are activated, enhanced activity must be correlated with altered active site conformation. The induced conformation model posits that the activated conformation for the active site of a given initiator caspase is attained through direct interaction with the adaptor protein complex or through homo-oligomerization facilitated by the adaptor protein complex.