Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | caspase-8 activation involves dimerization and subsequent interdomain autoprocessing of caspase-8 zymogens, mechanism, overview. The inactive caspase-8 paralogue FLIPL is able to activate caspase-8 by heterodimerization | Mus musculus |
Cloned (Comment) | Organism |
---|---|
expression of FK506-binding protein-caspase-8 fusion protein mutants in Escherichia coli BL21(DE3) as N-terminal His-tagged constructs using pET28b. Co-expression of caspase-8 and FLIPL in HeLa cells, the active-site cleft is restricted in caspase-8-FLIPL heterodimers | Mus musculus |
Protein Variants | Comment | Organism |
---|---|---|
D210A | site-directed mutagenesis, a solubilization mutant | Mus musculus |
D216A | site-directed mutagenesis, a solubilization mutant | Mus musculus |
D223A | site-directed mutagenesis, a solubilization mutant | Mus musculus |
F123Y | site-directed mutagenesis, a solubilization mutant | Mus musculus |
L122S | site-directed mutagenesis, a solubilization mutant | Mus musculus |
additional information | homodimerization fully activates both mature caspase-8 and the site-2 mutant, but fails to activate variants containing noncleavable mutations at site-1. The caspase-8 site-1 mutant is incapable of binding Z-VAD-fluoromethylketone when introduced into caspase-8-null NB7 cells, and stimulated to die via the extrinsic pathway. Elimination of the autoprocessing site of caspase-8 abrogates its pro-apoptotic function while leaving its proliferative function intact. Non-cleavable caspase-8-FLIPL heterodimer has attenuated activity on most apoptotic substrates, but shows high activity on HDAC-7 | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
Z-VAD-fluoromethylketone | i.e. benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone | Mus musculus |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | caspase-8 activation involves dimerization and subsequent interdomain autoprocessing of caspase-8 zymogens | Mus musculus |
Purification (Comment) | Organism |
---|---|
recombinant N-terminal His8-tagged FK506-binding protein-caspase-8 fusion protein mutants from Escherichia coli BL21(DE3) by nickel affinity and anion exchange chromatography | Mus musculus |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
BID + H2O | the cleavage sequences for caspase-8 are IEAD/S and LQTD/G | Mus musculus | ? | - |
? | |
FLIPL + H2O | the cleavage sequence for caspase-8 is LEVD/G | Mus musculus | ? | - |
? | |
HDAC-7 + H2O | the cleavage sequence for caspase-8 is LETD/G | Mus musculus | ? | - |
? | |
additional information | pro-caspase-6, linker, is a poor substrate fpr caspase-8 | Mus musculus | ? | - |
? | |
N-acetyl-IETD-4-trifluoromethylcoumarin 7-amide + H2O | - |
Mus musculus | N-acetyl-IETD + 7-amino-4-trifluoromethylcoumarin | - |
? | |
procaspase-10 + H2O | the cleavage sequence in procaspase-10, catalytically inactive C285A mutant, for caspase-8 is IEAD/A | Mus musculus | caspase-3 + ? | - |
? | |
procaspase-3 + H2O | the cleavage sequence in procaspase-3, catalytically inactive C285A mutant, for caspase-8 is IETD/S | Mus musculus | caspase-3 + ? | - |
? | |
procaspase-7 + H2O | the cleavage sequence in procaspase-7, catalytically inactive C285A mutant, for caspase-8 is IQAD/S | Mus musculus | caspase-3 + ? | - |
? | |
procaspase-8 + H2O | the autocleavage sequences of procaspase-8 monomers are VETD/S and LEMD/L, and of procaspase-8 dimers VETD/S and LEMD/L | Mus musculus | caspase-8 + ? | - |
? | |
RIPK1 + H2O | the cleavage sequence for caspase-8 is LQLD/C | Mus musculus | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | caspase-8 activation involves dimerization and subsequent interdomain autoprocessing of caspase-8 zymogens, overview. The catalytic domain of caspase-8 is crucial for its activity in the context of activation by homodimerization | Mus musculus |
Synonyms | Comment | Organism |
---|---|---|
caspase 8 | - |
Mus musculus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Mus musculus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Mus musculus |
General Information | Comment | Organism |
---|---|---|
malfunction | developmental abnormalities of caspase-8-deficient mice | Mus musculus |
physiological function | FADD-dependent formation of heterodimers between caspase-8 and FLIPL mediates the developmental role of caspase-8. The catalytic domain of caspase-8 is crucial for its activity in the context of activation by homodimerization. Mechanism of caspase-8 functional divergence in apoptotic and non-apoptotic pathways, overview | Mus musculus |