Caspase activation

Definition

Caspase activation refers to the process by which caspases, a family of cysteine proteases, are activated to initiate programmed cell death or apoptosis. This activation is crucial for maintaining cellular homeostasis and can be triggered by various signaling pathways, including intrinsic and extrinsic pathways, often involving the modification and targeting of proteins within the cell.

5 Must Know Facts For Your Next Test

1. Caspases exist as inactive precursors known as procaspases, which are activated through cleavage by other proteases or through dimerization in response to apoptotic signals.
2. There are two main pathways for caspase activation: the intrinsic pathway, which is triggered by cellular stress and mitochondrial signals, and the extrinsic pathway, which involves death receptors on the cell surface.
3. Caspase-3 is often referred to as an executioner caspase because it plays a key role in executing the death program once activated.
4. In addition to their role in apoptosis, caspases are also involved in other processes such as inflammation and cell differentiation, highlighting their importance beyond just cell death.
5. Caspase activation is tightly regulated by various inhibitors and proteins, such as IAPs (inhibitor of apoptosis proteins), ensuring that apoptosis occurs under appropriate conditions.

Review Questions

• How do intrinsic and extrinsic pathways lead to the activation of caspases, and what are their key differences?
  • Intrinsic and extrinsic pathways both lead to caspase activation but differ in their triggers. The intrinsic pathway is activated by internal signals such as DNA damage or stress, leading to mitochondrial release of cytochrome c, which then activates caspase-9. In contrast, the extrinsic pathway is initiated by external signals from death ligands binding to death receptors like Fas or TRAIL receptors on the cell surface, subsequently activating caspase-8. Both pathways converge on downstream executioner caspases like caspase-3 to facilitate apoptosis.
• Discuss the role of procaspases in the process of caspase activation and the significance of their cleavage.
  • Procaspases are inactive precursors that require cleavage to become active caspases. The cleavage event is crucial as it transforms procaspases into enzymatically active forms that can then execute apoptotic functions. For instance, when procaspase-9 is cleaved by apoptosomes in the intrinsic pathway, it becomes active and can further activate downstream effector caspases. This mechanism allows for amplification of the apoptotic signal, ensuring a robust response to pro-apoptotic stimuli.
• Evaluate the broader implications of dysregulated caspase activation in disease states such as cancer or neurodegeneration.
  • Dysregulated caspase activation can have significant implications in diseases like cancer and neurodegeneration. In cancer, improper inhibition of apoptosis can lead to uncontrolled cell proliferation and tumor growth as cancer cells evade programmed cell death. Conversely, excessive or inappropriate activation of caspases in neurodegenerative diseases can result in unwanted cell death, contributing to conditions like Alzheimer's or Parkinson's disease. Understanding these processes highlights potential therapeutic targets for modulating caspase activity to restore normal cellular functions.

Related terms

apoptosis: A form of programmed cell death that occurs in multicellular organisms, characterized by specific morphological changes and energy-dependent processes.

caspase cascade: A series of proteolytic events where active caspases activate additional caspases, amplifying the apoptotic signal and leading to cell death.

procaspase: The inactive precursor form of caspases that requires cleavage to become an active enzyme capable of executing apoptosis.