Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | engagement of Fas causes a rapid activation of caspase-8, induction of caspase-8 by Fas ligand, FasL, overview. Increased S-glutathionylation of Fas, caspase-8 activity, and cell death in cells lacking Grx1 | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
N-carbobenzyloxy-VAD-fluoromethyl ketone | a general caspase inhibitor, that effectively blocks FasL-induced cleavage of caspase-8 and completely prevents FasL-induced degradation of Grx1 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | initial activation of caspase-8 causes degradation of glutaredoxin-1, resulting in S-glutathionylation of Fas at cysteine 294, which subsequently enhances binding of FasL, aggregation of Fas, accumulation of Fas in lipid rafts, DISC assembly, and further activation of caspases, causing a propagation of apoptotic cell death. activation of caspases is required for degradation of glutaredoxin-1 and S-glutathionylation of Fas, engagement of Fas causes a rapid activation of caspase-8. Overexpression of Grx1 prevents increases in S-glutathionylation of Fas and attenuates caspase activation and apoptosis in response to receptor ligation. Cleaved caspase-8 and -3 demonstrate an association between active caspases and Grx1 in cells after ligation of Fas, whereas in control cells, these associations are not observed, regulation, overview | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | procaspase-8 is activated by cleavage to caspase-8 | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
C-10 cell | - |
Homo sapiens | - |
commercial preparation | recombinant enzyme | Homo sapiens | - |
epithelial cell | - |
Homo sapiens | - |
lung | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
glutaredoxin-1 + H2O | murine or human protein substrate, the putative cleavage site of caspase-8, amino acids 43-46 EFVD and 56-59 AIQD, which has predicted affiffinity toward glutamic and aspartic acid residues | Homo sapiens | ? | cleavage produces a 8 kDA fragment | ? | |
additional information | initial activation of caspase-8 causes degradation of glutaredoxin-1, resulting in S-glutathionylation of Fas at cysteine 294, which subsequently enhances binding of FasL, aggregation of Fas, accumulation of Fas in lipid rafts, DISC assembly, and further activation of caspases, causing a propagation of apoptotic cell death. activation of caspases is required for degradation of glutaredoxin-1 and S-glutathionylation of Fas, engagement of Fas causes a rapid activation of caspase-8. Overexpression of Grx1 prevents increases in S-glutathionylation of Fas and attenuates caspase activation and apoptosis in response to receptor ligation. Cleaved caspase-8 and -3 demonstrate an association between active caspases and Grx1 in cells after ligation of Fas, whereas in control cells, these associations are not observed, regulation, overview | Homo sapiens | ? | - |
? | |
additional information | caspases contain a reactive cysteine critical for enzymatic activity. Increased S-glutathionylation of Fas, caspase-8 activity, and cell death in cells lacking Grx1 | Homo sapiens | ? | - |
? |