What is the role of caspase 8 in apoptosis?

What is the role of caspase 8 in apoptosis?

Caspase-8 is a critical molecule as its absence leads to death of mice in utero. Upon activation, its main function is to promote apoptosis and, in thymus, apoptosis of negative selection is critical to eliminate autoaggressive T-cell clones that, if not eliminated, could contribute to develop autoimmune diseases.

What is the extrinsic apoptotic pathway?

In molecular biology, the words extrinsic pathway may refer to both the extrinsic pathway of apoptosis and the extrinsic pathway of blood coagulation. Extrinsic apoptosis pathway is one of the signal pathways which may trigger the process of programmed cell death namely cell apoptosis.

Is caspase 8 an effector caspase?

Caspase-8 is an effector in apoptotic death of dopaminergic neurons in Parkinson’s disease, but pathway inhibition results in neuronal necrosis. J Neurosci.

What is caspase pathway?

A group of intracellular proteases called caspases are responsible for the deliberate disassembly of the cell into apoptotic bodies during apoptosis. 1. Caspases are present as inactive pro-enzymes that are activated by proteolytic cleavage.

Is caspase-8 extrinsic?

Caspase-8 (CASP8) is a cysteine protease that plays a pivotal role in the extrinsic apoptotic signaling pathway via death receptors. Taken together, our findings demonstrate the precise cascade of CASP8-mediated apoptotic signals through the extrinsic pathway.

What triggers extrinsic pathway?

The extrinsic pathway is activated by external trauma that causes blood to escape from the vascular system. This pathway is quicker than the intrinsic pathway. It involves factor VII.

What is the difference between intrinsic and extrinsic pathways?

The intrinsic pathway is activated through exposed endothelial collagen, and the extrinsic pathway is activated through tissue factor released by endothelial cells after external damage. This pathway is the longer pathway of secondary hemostasis.

Why is caspase so named?

They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β.

Is caspase-9 intrinsic or extrinsic?

As the most intensively studied initiator caspase, caspase-9 is a key player in the intrinsic or mitochondrial pathway which is involved in various stimuli, including chemotherapies, stress agents and radiation.

What is the extrinsic pathway for caspase activation?

The extrinsic pathway (green arrows) is initiated by ligand binding to cell surface death receptors (TNF RI, Fas/CD95, DR3, TRAIL R1/DR4, TRAIL R2/DR5) followed by receptor oligomerization and cleavage of Pro-caspase-8 and -10. Activation of Caspase-8 and Caspase-10 results in the cleavage of BID and downstream effector caspases.

Besides it’s roles in triggering death receptor-mediated apoptosis, Caspase-8 has also been implicated in the onsets of anoikis, autophagy and pyroptosis. Furthermore, Caspase-8 also plays a crucial pro-survival function by inhibiting an alternative form of programmed cell death called necroptosis.

What happens to procaspase 8 at the disc?

As described above, the local concentration of procaspase-8 at the DISC leads to their autocatalytic activation and release of active caspase-8. Active caspase-8 then processes downstream effector caspases which subsequently cleave specific substrates resulting in cell death.

What is the extrinsic pathway for programmed cell death?

Extrinsic apoptosis pathway is one of the signal pathways which may trigger the process of programmed cell death namely cell apoptosis. Overview of Extrinsic Apoptosis Pathway.