EffektorKaspasen

EffektorKaspasen, also known as executioner caspases, are a subset of the caspase family that carry out the proteolytic dismantling of the cell during apoptosis. In humans the best characterized members are caspase-3, caspase-6 and caspase-7. They are produced as inactive zymogens (procaspases) and are activated by proteolytic cleavage in response to pro-apoptotic signals originating from either the intrinsic mitochondrial pathway or the extrinsic death-receptor pathway. Activation is typically carried out by initiator caspases such as caspase-8 or caspase-9, which cleave effector procaspases to generate active large and small subunits that assemble into active tetramers.

Once active, effector caspases cleave a broad set of cellular substrates, including structural proteins, DNA repair enzymes, and chromatin proteins, leading to the characteristic features of apoptosis such as DNA fragmentation, membrane blebbing, and cell shrinkage. A well-known substrate is PARP, whose cleavage helps commit the cell to death. The caspase cascade is tightly regulated by cellular inhibitors; IAP family members (the inhibitor XIAP) can block effector caspases, while mitochondria release SMAC/DIABLO to antagonize IAPs, promoting caspase activity.

Beyond apoptosis, effector caspases have been implicated in other cellular processes such as differentiation and certain forms of non-apoptotic cell remodeling, though their activity is typically associated with cell death. Dysregulation of effector caspases is linked to diseases including cancer, where reduced caspase activity enables survival of abnormal cells, and neurodegenerative diseases, where excessive caspase activation can contribute to neuronal loss. Therapeutic strategies have explored both inhibition and selective activation of effector caspases, but challenges include achieving specificity and avoiding unintended tissue damage.