Caspase Cleavage and Activation in Apoptosis

Caspases

Caspases are a family of cysteine proteases found in the cytosol that act as the primary mediators of apoptosis. Based on their role in apoptosis or inflammation, caspases are subdivided into apoptotic initiator caspases (Caspase-2, -8, -9, -10), apoptotic effector (executioner) caspases (Caspase-3, -6, -7), and inflammatory initiator caspases (Caspase-1, -4, -5, -11, 12L). 

Chart showing different types of caspases and their cleavage sites

All caspases are synthesized as inactive zymogens containing a variable length pro-domain followed by a large and small subunit. Cleavage of caspases occurs at specific asparagine (Asn) residues located after the pro-domain and in between the large and small subunits, and leads to the formation of active heterotetramers.

Initiator and effector caspase cleavage sites

Intrinsic or extrinsic death signals trigger the autocatalytic activation of apoptotic initiator caspases upon binding to dedicated protein complexes. Once activated, initiator caspases cleave the pro-forms of executioner caspases to activate them, which in turn are responsible for the proteolytic processing of various cellular proteins.

Caspase activity is regulated by many molecules including APAF-1, ARC, FLIP, and members of the inhibitor of apoptosis protein (IAP) family such as NAIP/BIRC1, cIAP-1/BIRC2, cIAP-2/BIRC3, XIAP/BIRC4, Survivin/BIRC5, and Livin/BIRC7. Explore the role of caspases in apoptosis with our Caspase Inhibitors

Inhibitors of Apoptosis (IAPs) - Products by Molecule

cIAP (pan)cIAP-1/HIAP-2cIAP-2/HIAP-1IAP InhibitorsLivinNAIP
SurvivinXIAP