Any feedback?
Literature summary for 3.4.22.61 extracted from
- From procaspase-8 to caspase-8: revisiting structural functions of caspase-8 (2010), J. Cell. Physiol., 225, 316-320.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | procaspase-8 activation via self-cleavage, overview | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | as a potential cell migration/adhesion factor, c-src blocks activation of caspase-8 through phosphorylating caspase-8 at Tyr380 | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | mature caspase-8 is released into cytosol. The signaling complex containing p62 and polyubiquitinated active caspase-8 translocates to cytosol to form the proapoptotic speckle called as aggresome to induce cell apoptosis in a p62-dependent manner | Homo sapiens | 5829 | - |
| additional information | Rab5 colocates with caspase-8 at integrin-rich regions such as focal adhesion, possibility of existence of caspase-8-c-src-p85a/caspase-8-p85a-c-src ternary complexes | Homo sapiens | - |
- |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| procaspase-8 + H2O | Homo sapiens | caspase-8 is initially synthesized as a single-chain zymogen, procaspase-8, and activated by autocleavage at proteolytic sites Asp126, Asp216, Asp374, and Asp384 after recruitment to DISCs by N-terminal two tandem DEDs of procaspase-8. The proximity-driven dimerization of procaspase-8 is attributable to initiate autocleavage of procaspase-8 involving intra-dimeric and inter-dimeric attack. Dimerized procaspase-8 which achieves enzymatical competency specifically processes one another, while mature caspase-8 can cleave effector caspases and some other substrates. Dramatical conformation changes of the linker region undergo in order to bring cleavage sites, Asp374 and Asp384, to the vicinity of catalytic residue Cys283 from other protomer during dimerization of procaspase-8. Separation of the large and small subunit after intra-dimeric cleavage in the linker region between the large and small subunit renders the linker region between the large subunit and the prodomain of caspase-8 susceptible for the further inter-dimeric cleavage | caspase-8 + ? | the C- and N-terminal end, of linker region are released with cleavage at Asp374 and Asp384 before separation of the large and small subunit | ? |  |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | as a potential cell migration/adhesion factor, c-src blocks activation of caspase-8 through phosphorylating caspase-8 at Tyr380 | Homo sapiens |
| proteolytic modification | caspase-8 is initially synthesized as a single-chain zymogen, procaspase-8, and activated by autocleavage at proteolytic sites Asp126, Asp216, Asp374, and Asp384 after recruitment to DISCs by N-terminal two tandem DEDs of procaspase-8. The proximity-driven dimerization of procaspase-8 is attributable to initiate autocleavage of procaspase-8 involving intra-dimeric and inter-dimeric attack | Homo sapiens |
| side-chain modification | ubiquitination is specific for caspase-8 in a CUL3-dependent manner. CUL3 is recruited to DISCs at the early stage of extrinsic apoptotic pathway to ubiquitinate caspase-8. Polyubiquitination of caspase-8 is partially ascribed to initiation and conformational changes in the activation process of procaspase-8 | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| procaspase-8 + H2O | caspase-8 is initially synthesized as a single-chain zymogen, procaspase-8, and activated by autocleavage at proteolytic sites Asp126, Asp216, Asp374, and Asp384 after recruitment to DISCs by N-terminal two tandem DEDs of procaspase-8. The proximity-driven dimerization of procaspase-8 is attributable to initiate autocleavage of procaspase-8 involving intra-dimeric and inter-dimeric attack. Dimerized procaspase-8 which achieves enzymatical competency specifically processes one another, while mature caspase-8 can cleave effector caspases and some other substrates. Dramatical conformation changes of the linker region undergo in order to bring cleavage sites, Asp374 and Asp384, to the vicinity of catalytic residue Cys283 from other protomer during dimerization of procaspase-8. Separation of the large and small subunit after intra-dimeric cleavage in the linker region between the large and small subunit renders the linker region between the large subunit and the prodomain of caspase-8 susceptible for the further inter-dimeric cleavage | Homo sapiens | caspase-8 + ? | the C- and N-terminal end, of linker region are released with cleavage at Asp374 and Asp384 before separation of the large and small subunit | ? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | dramatical conformation changes of the linker region undergo in order to bring cleavage sites, Asp374 and Asp384, to the vicinity of catalytic residue Cys283 from other protomer during dimerization of procaspase-8 | Homo sapiens |
| More | the C- and N-terminal end are necessary to stabilize dimer of caspase-8 and induce separation of the large and small subunit | Homo sapiens |
| tetramer | dimer of dimers, separation of the large and small subunit after intra-dimeric cleavage in the linker region between the large and small subunit renders the linker region between the large subunit and the prodomain of caspase-8 susceptible for the further inter-dimeric cleavage. Under apoptotic stimuli, caspase-8 undergoes catalytic autocleavage to generate the proapoptotic mature tetramer to induce apoptosis | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | cells lacking in caspase-8 show reduced adhesion to fibronectin with concomitant reduction in adhesion-induced ERK 1/2 activation, these effects can be restored upon reexpression of either the wild-type or catalytically inactive point mutant protein, implying caspase-8 is involved to promote cell adhesion and adhesion-induced ERK 1/2 activation independently of its catalytical activity | Homo sapiens |
| metabolism | the interaction of phosphorylated caspase-8 with regulatory subunit, p85alpha, of phosphatidylinositol-3-OH kinase enhances Rac activation to promote cell migration, requiring Tyr380 and phosphorylation by c-src | Homo sapiens |
| physiological function | mature caspase-8 cleaves a huge number of different cellular substrates in the cytosol. Under apoptotic stimuli, caspase-8 undergoes catalytic autocleavage to generate the proapoptotic mature tetramer to induce apoptosis | Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
