Inhibitors | Comment | Organism | Structure |
---|---|---|---|
FLIPL protein | i.e. FLICE-like inhibitory protein long, inhibits apoptotic caspase 8 activation. FLIP is homologous to caspase 8 but lacks catalytic residues. FLIP forms a heterodimer with caspase 8, which prevents apoptosis induction. Dynamic ubiquitylation is at least partially responsible for controlling the activation of caspase 8 by FLIPL | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
RIPK1 + H2O | Homo sapiens | Lys63-linked RIPK1 ubiquitylation is required to render RIPK1 susceptible to caspase 8-mediated cleavage, the mechanism by which RIPK1 signalling is suppressed in this context | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | caspase proenzymes are induced to dimerize, and this dimerization leads to enzyme activation, mechanism of caspase 8 activation, detailed overview. In the case of caspase 8, dimerization is followed by interdomain cleavage events, first between the large and small subunits and subsequently between the large subunit and the prodomain. These cleavage events stabilize the caspase 8 homodimer and remove the prodomain, leading to formation of a fully active enzyme composed of two large and two small subunits | Homo sapiens |
side-chain modification | both degradative and non-degradative ubiquitylation have central roles in the control of nuclear factor-kappaB activation, as well as caspase 8 and receptor-interacting protein kinase 1, RIPK1, signalling, overview. Caspase 8 is modified by non-degradative ubiquitin chains allowing the activation of a non-cleavable caspase 8 mutant. Dynamic ubiquitylation is at least partially responsible for controlling the activation of caspase 8 by FLICE-like inhibitory protein long, FLIPL | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
T-lymphocyte | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
RIPK1 + H2O | - |
Homo sapiens | ? | - |
? | |
RIPK1 + H2O | Lys63-linked RIPK1 ubiquitylation is required to render RIPK1 susceptible to caspase 8-mediated cleavage, the mechanism by which RIPK1 signalling is suppressed in this context | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | caspase proenzymes are induced to dimerize, and this dimerization leads to enzyme activation. In the case of caspase 8, dimerization is followed by interdomain cleavage events, first between the large and small subunits and subsequently between the large subunit and the prodomain. These cleavage events stabilize the caspase 8 homodimer and remove the prodomain, leading to formation of a fully active enzyme composed of two large and two small subunits | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
caspase 8 | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | proliferative defects of caspase 8-deficient T cells and B cells. Caspase-8 deficiency causes programmed necrotic cell death | Homo sapiens |
metabolism | recruitment of caspase 8 and FLIP to a RIPK1-containing complex determines cell fate, overview | Homo sapiens |
physiological function | caspase 8 can initiate apoptosis in response to cell surface receptor activation, but it is also required for embryonic development and immune cell proliferation, defined by suppression of receptor-interacting protein kinase 3, a kinase that triggers an alternative form of cell death called programmed necrosis. The extrinsic apoptosis, is mediated by a group of receptors of the tumour necrosis factor, TNF, superfamily called the death receptors. Caspase 8 is further implicated in cell motility, metastasis, and suppression of inflammation. The non-apoptotic roles of FADD and caspase 8 are involved the suppression of RIPK3-dependent programmed necrosis, the caspase 8FLIP heterodimer is implicated in carrying out the suppression of RIPK3 signalling. Mechanism of caspase 8 activation, detailed overview | Homo sapiens |