caspase complex

Definition

Target type: cellularcomponent

A protein complex that contains one or more cysteine-type endopeptidases (also called caspases), which give the complex a peptidase activity with specificity for the hydrolysis of aspartyl bonds. These complexes may be involved e.g. in apoptotic or inflammation processes. [GOC:cna, GOC:mtg_apoptosis, PMID:15569692]

The caspase complex is a multi-protein assembly that plays a central role in programmed cell death, also known as apoptosis. It is composed of several key components, including:

1. **Caspases:** These are the main enzymatic effectors of apoptosis. Caspases are cysteine proteases, meaning they use a cysteine residue in their active site to cleave peptide bonds. They exist in inactive pro-caspase forms and are activated through proteolytic cleavage. Activation of caspases triggers a cascade of proteolytic events, leading to dismantling of cellular components and ultimately cell death.

2. **Apoptotic adaptor proteins:** These proteins link caspases to upstream death signals. Some important adaptor proteins include:
* **Apaf-1 (Apoptotic protease-activating factor 1):** Forms the apoptosome, a platform for caspase-9 activation in response to mitochondrial signals.
* **FADD (Fas-associated death domain protein):** Recruits caspase-8 to death receptors, initiating the extrinsic apoptotic pathway.
* **TRADD (Tumor necrosis factor receptor type 1-associated DEATH domain):** Acts as an adaptor protein for the TNF receptor family.

3. **Mitochondrial components:** The mitochondria play a crucial role in apoptosis by releasing apoptogenic factors, including cytochrome c, into the cytosol.
* **Cytochrome c:** Binds to Apaf-1, leading to apoptosome formation and activation of caspase-9.
* **Smac/DIABLO (Second mitochondria-derived activator of caspase/Direct IAP-binding protein with low pI):** Inhibits inhibitor of apoptosis proteins (IAPs), which normally block caspase activity.

4. **Inhibitor of apoptosis proteins (IAPs):** These proteins regulate caspase activity by directly binding to and inhibiting them.

The caspase complex assembles in a tightly regulated manner, ensuring that apoptosis is initiated only when necessary. The specific components and their interactions vary depending on the apoptotic pathway (intrinsic or extrinsic) and the cell type.

In the **intrinsic apoptotic pathway**, caspase activation is triggered by mitochondrial signals, often in response to cellular stress. The release of cytochrome c from the mitochondria leads to the formation of the apoptosome, which activates caspase-9. Caspase-9 then activates downstream executioner caspases, such as caspase-3 and caspase-7, which execute the dismantling of the cell.

In the **extrinsic apoptotic pathway**, caspase activation is initiated by death receptors on the cell surface. Ligand binding to these receptors leads to the recruitment of adaptor proteins, such as FADD and TRADD, which bring together caspase-8 and caspase-10. These initiator caspases then activate the executioner caspases, leading to apoptosis.

The caspase complex represents a critical point of convergence for apoptotic signals, ensuring that cell death is a tightly controlled and irreversible process.'
"

Proteins (1)

Compounds (18)