How do initiator caspases get activated?

Initiator caspases are activated by intrinsic and extrinsic apoptopic pathways. This leads to the activation of other caspases including executioner caspases that carry out apoptosis by cleaving cellular components.

What is the function of the initiator caspase?

Initiator caspases activate executioner caspases that subsequently coordinate their activities to demolish key structural proteins and activate other enzymes. The morphological hallmarks of apoptosis result, including DNA fragmentation and membrane blebbing.

How does apoptosome activate caspase?

The results demonstrate that the Apaf-1 apoptosome activates caspase-9 by two means: suppressing the inhibition mediated by the caspase recruitment domains (CARD) domain and stimulating the catalytic activity of the protease domain.

How do I activate my caspases?

All caspases are synthesized in cells as catalytically inactive zymogens, and must undergo an activation process. The activation of an effector caspase, such as caspase-3 or -7, is performed by an initiator caspase, such as caspase-9, through an internal cleavage to separate the large and small subunits.

How is caspase-3 activated?

Caspase-3 is a cysteine–aspartic acid protease that cleaves cellular targets and executes cell death. Our current understanding is caspase-3 is activated by the cleavage of the interdomain linker and then subsequent cleavage of the N-terminal prodomain.

What is the function of caspase-3?

Caspases are crucial mediators of programmed cell death (apoptosis). Among them, caspase-3 is a frequently activated death protease, catalyzing the specific cleavage of many key cellular proteins.

Do caspases cleave DNA?

1. Regulation of DNA fragmentation by phosphorylation of the MAPK family and mitochondrial proteins. Cleaved caspase-3 translocates to the nucleus, where it cleaves substrates such as the DNA repair enzyme PARP and ICAD. Cleavage of ICAD results in the release and activation of CAD, which induces DNA fragmentation.

How are caspases regulated?

Caspases are synthesized within the cell as inactive zymogens that lack significant protease activity. Thus, caspases are, in essence, regulated from the moment of protein synthesis in that they are not activated until receipt of specific death stimuli (Earnshaw et al.

Is caspase activation reversible?

Caspases mediate apoptotic signal transduction by cleavage of apoptosis-implicated proteins and the caspases themselves. In the process of caspase activation, reversible protein phosphorylation plays an important role.

What is the apoptosis pathway?

The intrinsic and extrinsic pathways of apoptosis are both naturally occurring processes by which a cell is directed to programmed cell death. Both pathways of apoptosis activate cell signaling cascades that are an indispensable part of the development and function of an organism.

Which is the initiator of the caspase signaling cascade?

Caspase-8, caspase-10 and caspase-9 are believed to be the initiator caspases at the top of the caspase signaling cascade. Recruitment of caspases to DISC and apoptosome leads to their activation by dimer formation.

How are caspases activated in the apoptosome?

Initiator caspases are activated in three distinct protein complexes, the death-inducing signaling complex (DISC; Caspase-8 and -10), the apoptosome (Caspase-9), and the PIDDosome (Caspase-2). The DISC is formed following ligand binding and death receptor oligomerization.

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.

What are the different types of caspases in mammals?

Mammalian caspases can be subdivided into three functional groups, apoptotic initiator caspases (Caspase-2, -8, -9, -10), apoptotic effector caspases (Caspase-3, -6, -7), and caspases involved in inflammatory cytokine processing (Caspase-1, -4, -5, 11, and -12L/12S).

How do initiator caspases get activated? Initiator caspases are activated by intrinsic and extrinsic apoptopic pathways. This leads to the activation of other caspases including executioner caspases that carry out apoptosis by cleaving cellular components. What is the function of the initiator caspase? Initiator caspases activate executioner caspases that subsequently coordinate their activities to demolish…