Which are the initiator caspases?
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.
Is caspase-8 an initiator caspase?
Caspases are a family of cysteine proteases that work in the apoptosis and inflammation signaling pathways. Caspases are divided into two classes, initiator and effector, and caspase-8 is a representative initiator caspase.
Which caspase is the initiator of apoptosis?
CED-3 in C. elegans is both the initiator and the effector caspase. The executioners of apoptosis are caspases, a family of conserved cysteine proteases that usually cleave after an aspartate residue in their substrates (Thornberry and Lazebnik 1998).
Is caspase-9 an initiator caspase?
Caspase-9, the essential initiator caspase required for apoptosis signalling through the mitochondrial pathway, is activated on the apoptosome complex, and failure to activate caspase-9 has profound pathophysiological consequences.
How is an initiator caspase 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.
Which amino acids are associated with caspase?
Caspases are a family of cysteine proteases that cleave proteins following aspartic acid residues. These proteases exist in a hierarchy with upstream caspases 2, 8, 9, and 10 and downstream caspases 3, 6, and 7.
What is the substrate of caspase-8?
Table 1
| Enzyme | Peptide substratea | Protein substrateb |
|---|---|---|
| Caspase-6 | VQVD | VEVD |
| Caspase-7 | DEVD | DEVD |
| Caspase-8 | LETD | XEXD |
| Caspase-9 | (W/L)EHD | − |
How does caspase-3 cause apoptosis?
Caspase-3 is known as an executioner caspase in apoptosis because of its role in coordinating the destruction of cellular structures such as DNA fragmentation or degradation of cytoskeletal proteins (1). The activity of caspase-3 is tightly regulated and it is produced as zymogen in an inactive pro-form (1).
Which caspase is associated with Apoptosome?
The mature caspase-9–activating complex or apoptosome consists of an APAF-1 septamer, with each APAF-1 molecule able to recruit and activate dimers of caspase-9. Once activated, caspase-9 cleaves and activates the executioner caspases 3, 6, and 7.
How is Procaspase 9 activated?
Caspase-9 is activated by binding to Apaf-1, a multidomain adapter protein containing an N-terminal caspase recruitment domain (CARD), followed by a nucleotide-binding and oligomerization domain [13–16].
What is the role of the initiator caspases?
Initiator caspases initiate the apoptosis signal while the executioner caspases carry out the mass proteolysis that leads to apoptosis. Initially synthesized as inactive pro-caspases, caspases become rapidly cleaved and activated in response to granzyme B, death receptors, and apoptosome stimuli.
What is the function of caspases?
Caspases (cysteine-aspartic proteases) are proteolytic enzymes largely known for their role in controlling cell death and inflammation.
Which is the initiator caspase in apoptosis?
In mitochondrion-dependent apoptosis, release of cytochrome C into the cytosol results in the formation of apoptosome containing cytochrome C, Apaf-1 and caspase-9. Caspase-8, caspase-10 and caspase-9 are believed to be the initiator caspases at the top of the caspase signaling cascade.
How does the initiator caspases antibody sampler kit work?
Each antibody in the Initiator Caspases Antibody Sampler Kit recognizes its respective target at endogenous levels. Caspase-3 (D3R6Y) Rabbit mAb detects full-length caspase-3 (35 kDa) as well as the large subunit (p20) of caspase-3 resulting from cleavage during apoptosis.
What’s the difference between initiator and executioner caspases?
Initiator caspases auto-proteolytically cleave whereas Executioner caspases are cleaved by initiator caspases. This hierarchy allows an amplifying chain reaction or cascade for degrading cellular components, during controlled cell death.
How are the prodomains of a caspase activated?
Depending on the structure of their prodomains, caspases are activated by different mechanisms. Long prodomain-containing initiator caspases exist as inactive monomers and are activated by proximity-induced dimerization which can sometimes be facilitated by adaptor proteins.