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Literature summary for 3.4.22.61 extracted from

  • Pop, C.; Oberst, A.; Drag, M.; Van Raam, B.J.; Riedl, S.J.; Green, D.R.; Salvesen, G.S.
    FLIP(L) induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity (2011), Biochem. J., 433, 447-457.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.22.61

Activating Compound

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(Commentary)

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

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

Inhibitors Comment Organism Structure
Z-VAD-fluoromethylketone i.e. benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone Mus musculus

Organism

Organism UniProt Comment Textmining
Mus musculus
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification caspase-8 activation involves dimerization and subsequent interdomain autoprocessing of caspase-8 zymogens Mus musculus

Purification (Commentary)

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 and Products (Substrate)

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

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

Synonyms Comment Organism
caspase 8
-
 Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Mus musculus

General Information

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