What are the initiator and effector caspases? Give examples of each

Caspases are a special family of protease enzymes that play a very important role in apoptosis, which is also known as programmed cell death. These enzymes are present in an inactive form inside the cell and get activated when the cell receives a signal to die. Caspases work like a chain reaction. Some caspases get activated first and then they activate other caspases. Based on their function in the apoptosis process, caspases are mainly divided into two groups: initiator caspases and effector caspases. Both types work together to ensure proper and controlled death of damaged or unnecessary cells in the body.

1. Initiator Caspases:

Initiator caspases are the first enzymes to be activated when the cell receives a death signal. These caspases act like a starting point in the apoptotic pathway. They do not break down the cell directly but instead activate other caspases (effector caspases) by cutting them at specific places. Initiator caspases are usually activated through multi-protein complexes. For example, in the extrinsic pathway, initiator caspases are activated through death receptor complexes like DISC (Death-Inducing Signaling Complex), and in the intrinsic pathway, they are activated by the apoptosome.

Examples of initiator caspases:

  • Caspase-8:
    • Caspase-8 is activated in the extrinsic pathway when death receptors like Fas or TNF receptor are stimulated by their ligands. Once activated, it cleaves and activates downstream effector caspases like caspase-3, initiating the execution phase of apoptosis.
  • Caspase-9:
    • Caspase-9 is involved in the intrinsic pathway and becomes active after the release of cytochrome c from mitochondria. It forms a complex with Apaf-1 and ATP to create the apoptosome, which activates effector caspases to begin cell dismantling.

2. Effector Caspases:

Effector caspases are also known as executioner caspases because they are directly responsible for breaking down the important components of the cell. Once they are activated by initiator caspases, they start cleaving various structural and regulatory proteins inside the cell, leading to the classic features of apoptosis like DNA fragmentation, chromatin condensation and cell membrane blebbing.

Examples of effector caspases:

  • Caspase-3:
    • Caspase-3 is a major executioner caspase that is activated by both intrinsic and extrinsic pathways. It cleaves several important substrates like PARP, leading to DNA fragmentation, nuclear condensation and other typical apoptotic changes in the cell.
  • Caspase-7:
    • Caspase-7 works alongside caspase-3 and is also activated by initiator caspases. It targets structural proteins in the cytoskeleton and nuclear membrane, playing a key role in dismantling the cell in a controlled and clean manner during apoptosis.






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