Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | caspase-8 integration into cardiolipin-rich domains of the outer mitochondrial membrane results in full activation of this caspase which can then directly access and cleave its substrate Bid | Homo sapiens |
General Stability | Organism |
---|---|
caspase-8 polyubiquitination by the E3 ligase cullin-3 and its subsequent p62-dependent aggregation stabilises active caspase-8 | | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
cFLIP | high levels of cFLIP can abrogate caspase-8 activation at the DISC | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytoplasm | caspase-8/cullin-3/p62 complex is translocates to the cytosol from where it induces apoptosis in a p62-dependent manner | Homo sapiens | 5737 | - |
mitochondrion | the mitochondrial membrane protein Cardif plays a role in caspase-8 translocation to mitochondria. The anionic mitochondria-specific phospho-lipid cardiolipin acts as a mitochondria-associated platform that is actually required for caspase-8 translocation in type II cells | Homo sapiens | 5739 | - |
additional information | following caspase-8 recruitment to the DISC, cullin-3 is able to ubiquitinate caspase-8 which in turn recruits the ubiquitin-binding protein p62 | Homo sapiens | - |
- |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
Bid + H2O | Homo sapiens | Bid is a caspase-8 substrate and that its cleavage can be crucial for CD95-induced apoptosis. Caspase-8-mediated cleavage of Bid into a pro-apoptotically active, truncated form provides the link between death receptor stimulation and mitochondrial apoptotic events | tBid + ? | - |
? | |
FLIPL protein + H2O | Homo sapiens | - |
? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | proteolytic cleavage is required to fully activate caspase-8 so that it can cleave apoptotic substrates like caspase-3 and Bid. Dimerisation of procaspase-8 provides proteases only with a limited substrate repertoire limited to itself, probably caspase-10, and cFLIP | Homo sapiens |
side-chain modification | caspase-8 polyubiquitination by the E3 ligase cullin-3 and its subsequent p62-dependent aggregation stabilises active caspase-8 and thereby positively regulates apoptosis | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
Bid + H2O | Bid is a caspase-8 substrate and that its cleavage can be crucial for CD95-induced apoptosis. Caspase-8-mediated cleavage of Bid into a pro-apoptotically active, truncated form provides the link between death receptor stimulation and mitochondrial apoptotic events | Homo sapiens | tBid + ? | - |
? | |
Bid + H2O | caspase-8 cleaves Bid at Asp60 leading to the release of a truncated form containing the C-terminal part of the protein, 15 kDa. Cleavage of Bid by caspase-8 removes the N-terminal portion of the protein which, when still linked to the C-terminal p15 portion inhibits the pro-apoptotic function of the latter | Homo sapiens | tBid + ? | - |
? | |
FLIPL protein + H2O | - |
Homo sapiens | ? | - |
? |
General Information | Comment | Organism |
---|---|---|
malfunction | in p62-deficient cancer cells caspase-8 activity and apoptosis are diminished, yet not abrogated | Homo sapiens |
metabolism | caspase-8 and Bid are the known procurers of the death signal leading from death receptor stimulation to permeabilisation of the outer mitochondrial membrane in the apoptotic pathway, regulation of caspase-8 and Bid function and activation, overview | Homo sapiens |
additional information | following caspase-8 recruitment to the DISC, the E3 ligase cullin-3 is able to ubiquitinate caspase-8 which in turn recruits the ubiquitin-binding protein p62, caspase-8 polyubiquitination by cullin-3 and its subsequent p62-dependent aggregation stabilises active caspase-8 and thereby positively regulates apoptosis. The caspase-8/cullin-3/p62 complex is translocates to the cytosol from where it induces apoptosis in a p62-dependent manner | Homo sapiens |
physiological function | DISC-activated caspase-8 and -10 trigger a caspase cascade by cleavage of caspase-3. Caspase-8 and Bid are the known procurers of the death signal leading from death receptor stimulation to permeabilisation of the outer mitochondrial membrane in the apoptotic pathway, regulation of caspase-8 and Bid function and activation, overview. In type II cells activation of the mitochondrial arm of the apoptosis pathway is required for the induction of apoptosis following a death receptor stimulus. The bridging element between the two arms of the apoptosis pathway is the caspase-8-mediated cleavage of the pro-apoptotic Bcl-2 family member Bid. The anionic mitochondria-specific phospho-lipid cardiolipin acts as a mitochondria-associated platform that is actually required for caspase-8 translocation, oligomerisation and activation after CD95 stimulation, and hence CD95-induced death in type II cells. In type I cells caspase-8 activation at the DISC is very efficient, resulting in direct activation of caspase-3 and the caspase cascade | Homo sapiens |