CASP8 encodes caspase-8, an aspartate-directed cysteine endopeptidase with tandem N-terminal death-effector domains. FADD-dependent recruitment organizes procaspase-8 in death-inducing and related cytosolic signaling complexes, promoting dimerization and context-dependent proteolytic processing. Its substrates include effector procaspases, BID, RIPK1 and gasdermin C: cleavage can initiate apoptosis, restrain RIPK-dependent necroptosis or promote inflammatory membrane damage in different cellular settings. CASP8 acts upstream of CASP3 in some GSDME-processing pathways, while the gasdermin supplies the pore-forming activity. Nonapoptotic functions include regulation of immune-cell activation, monocyte differentiation and phosphorylation-dependent migration. Human CASP8 deficiency causes combined defects in lymphocyte apoptosis and immune activation. Alternative products include catalytic-domain-deficient forms that can modulate death-receptor signaling; activity and localization therefore depend on product, complex and stimulus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001525 angiogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the curated mouse-to-human angiogenesis assertion as a contextual role. Reason: The ISS assertion is a curated orthology transfer, not a claim that CASP8 is an angiogenic ligand. Its mouse donor experiment has not been independently reconstructed. The target literature also reports CASP8/cFLIPL participation in TRAIL-associated angiogenic signaling; the precise catalytic versus scaffold contribution remains context dependent. No new human angiogenesis assertion or independent angiogenic core is proposed. Supporting Evidence: |
| GO:0001817 regulation of cytokine production | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CASP8 modulates cytokine production in inflammatory complexes. Reason: The existing mouse-derived assertion is consistent with CASP8-associated inflammatory complexes and pro-IL1B processing. Direct cytokine-precursor cleavage and upstream transcriptional signaling are distinct mechanisms; the accessible Dectin-1 abstract does not establish the species of every assay. Retain the broad regulatory context without claiming every cytokine is a CASP8 substrate. |
| GO:0001817 regulation of cytokine production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CASP8 modulates cytokine production in inflammatory complexes. Reason: The existing mouse-derived assertion is consistent with CASP8-associated inflammatory complexes and pro-IL1B processing. Direct cytokine-precursor cleavage and upstream transcriptional signaling are distinct mechanisms; the accessible Dectin-1 abstract does not establish the species of every assay. Retain the broad regulatory context without claiming every cytokine is a CASP8 substrate. |
| GO:0002682 regulation of immune system process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain broad regulation of immune-system processes. Reason: Broadness does not make the ARBA inference biologically wrong. Human CASP8 deficiency impairs T-, B- and NK-cell activation, while inflammatory complexes use its protease and recruitment functions. These support this existing high-level regulatory assertion without making all immune outcomes independent core functions. |
| GO:0004175 endopeptidase activity | IEA GO_REF:0000107 | MODIFY | Summary: Refine broad peptidase activity to cysteine-type endopeptidase activity. Reason: CASP8 catalyzes internal peptide-bond cleavage after aspartate. Its measured proteolysis and curated specificity support the existing narrower endopeptidase term; the original donor/domain assertion remains intact. This refinement does not imply that the short catalytic-domain-deficient products retain enzymatic activity. Proposed replacements: cysteine-type endopeptidase activity |
| GO:0004197 cysteine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The conserved CASP8 cysteine endopeptidase activity is supported. Reason: The PAINT assertion is consistent with direct CASP8 substrate cleavage, including RIPK1 and GSDMC. The presence of CASP8 itself among descendant evidence is expected, not circular. The ancestral PTN placement and full alignment were not independently inspected; there is no target-specific loss argument against this catalytic function. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16916640 Engineered hybrid dimers: tracking the activation pathway of... | ACCEPT | Summary: CASP8 directly cleaves and activates recombinant procaspase-7. Reason: Although the cached abstract foregrounds caspase-7, the author-hosted primary Results, Figure 1 caption and Methods explicitly assay recombinant DED-deleted caspase-8 against procaspase-7 activation-site mutants. Caspase-8-alone substrate turnover was controlled. The high-salt and engineered-protein conditions are not a measurement of native DISC kinetics. The evidence-anchor appendix in CASP8-notes.md records the external Figure 1C passage and primary PDF URL; the canonical cache remains abstract-only. Supporting Evidence: |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16920334 Protective role of Cop in Rip2/caspase-1/caspase-4-mediated ... | ACCEPT | Summary: Retain the experimentally curated CASP8 endopeptidase assertion. Reason: The accessible abstract emphasizes COP/RIP2/caspase-1/4, and the CASP8-specific control in the full paper remains uninspected. This is not evidence of a paralog error. Independent target-specific cleavage experiments establish precisely the same CASP8 molecular function, so acceptance defers to the experimental curator without claiming the original target assay was reverified. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:19240112 Huntingtin promotes cell survival by preventing Pak2 cleavag... | ACCEPT | Summary: CASP8 proteolysis is compatible with the PAK2 substrate study. Reason: The target source reports protection of PAK2 from caspase-3 and caspase-8 cleavage in cellular and in-vitro assays. Retain the curated catalytic assertion, distinguishing substrate protection by huntingtin from a CASP8 survival function and without transferring every PAK2 phenotype to CASP8. Supporting Evidence: |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:31827280 A dominant autoinflammatory disease caused by non-cleavable ... | ACCEPT | Summary: CASP8 cleaves RIPK1 at its regulated cleavage site. Reason: Human cleavage-resistant RIPK1 variants and biochemical cleavage evidence establish the relevant CASP8 proteolytic reaction. Patient cells and mouse models provide distinct context; the outcome varies across cell types and is not uniformly suppression of every TNF response. Supporting Evidence: |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:32929201 PD-L1-mediated gasdermin C expression switches apoptosis to ... | ACCEPT | Summary: CASP8 directly cleaves GSDMC. Reason: The human GSDMC substrate experiments combine recombinant cleavage, CASP8 perturbation and cleavage-resistant GSDMC. CASP6 also cleaves GSDMC in vitro, so the cellular CASP8 result does not establish unique enzyme specificity under all conditions. Gasdermin, rather than CASP8, forms the membrane pore. Supporting Evidence: |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:33852854 Gasdermin E permits interleukin-1 beta release in distinct s... | ACCEPT | Summary: Retain CASP8 endopeptidase activity in the inflammasome-associated caspase cascade. Reason: The source distinguishes human THP-1 from mouse macrophage systems and detects apoptotic-caspase activation when GSDMD is absent. GSDME processing is attributed to CASP3; this annotation is not evidence that CASP8 directly cleaves GSDME. Independent CASP8 substrate assays corroborate the molecular function. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:34012073 The metabolite Ξ±-KG induces GSDMC-dependent pyroptosis throu... | ACCEPT | Summary: DR6-associated CASP8 proteolysis can activate GSDMC. Reason: The source describes metabolite-induced DR6 endocytosis, CASP8 activation and GSDMC cleavage in the tested cancer-cell/model settings. Accept the enzyme activity without equating the metabolic perturbation with every physiological death-receptor response. Supporting Evidence: |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:35594856 Human NLRP1 is a sensor of pathogenic coronavirus 3CL protea... | ACCEPT | Summary: CASP8 acts upstream of CASP3 during coronavirus-associated GSDME processing. Reason: Human lung-cell experiments detect CASP8 processing and use a CASP8 inhibitor alongside CASP3/GSDME genetic perturbations. These support the curated caspase activity, with the limit that CASP8 was not genetically isolated in the selected assay and CASP3 performs the assigned GSDME cleavage. Supporting Evidence: |
| GO:0004197 cysteine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic mappings agree with the established CASP8 catalytic activity. Reason: The domain, rule and ortholog sources converge on a target-specific activity established by substrate assays. No functional loss is inferred from the multiple source methods, and the short products lacking the catalytic domain are not assumed to perform this reaction. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts... | ACCEPT | Summary: CASP8 cleaves RIP1 during TNF signaling. Reason: The accessible source identifies RIP1 cleavage and its impact on NF-kappaB and death signaling. Its nominal full-text cache contains only a short abstract-like body, so the complete original controls were not inspected. The curated IMP assertion is corroborated by independent human RIPK1 cleavage evidence. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:11717445 Caspase-10 is an initiator caspase in death receptor signali... | ACCEPT | Summary: Retain CASP8 catalytic participation in death-receptor signaling. Reason: The abstract explicitly compares CASP8 and CASP10 despite its CASP10 title. It supports their FADD-associated death-effector-domain signaling; the CASP8-specific enzymatic controls are not fully visible in the cache. Independent direct CASP8 cleavage studies corroborate this established molecular function. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containi... | ACCEPT | Summary: Ripoptosome-associated CASP8 proteolysis regulates cell-death outcomes. Reason: Human keratinocyte experiments separate CASP8- and RIP3-dependent death responses and show cFLIP-dependent complexes and cleavage. Retain the enzyme function without treating the proposed route of complex disassembly as a completely resolved mechanism. Supporting Evidence: |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:21980415 Identification of a conserved anti-apoptotic protein that mo... | ACCEPT | Summary: Retain the experimentally curated CASP8 catalytic activity. Reason: The CAAP perturbation study reports activation of caspases including CASP8 in human cell lines. Simultaneous activation does not establish that CASP8 alone produces the entire phenotype; nevertheless the activity itself is independently established and the experimental annotation is not contradicted. |
| GO:0004197 cysteine-type endopeptidase activity | TAS PMID:8681376 Involvement of MACH, a novel MORT1/FADD-interacting protease... | ACCEPT | Summary: The original MACH/CASP8 cloning study supports its protease function. Reason: The source distinguishes catalytically competent products from incomplete isoforms that antagonize death-receptor signaling. Retain the gene-level catalytic annotation while preserving all nine machine product mappings and avoiding universal activity across them. Supporting Evidence: |
| GO:0004197 cysteine-type endopeptidase activity | TAS Reactome:R-HSA-2562564 | ACCEPT | Summary: CASP8 catalytic activity operates in cytosolic death-regulatory complexes. Reason: The specific Reactome event describes CASP8 processing or substrate cleavage within a TLR-associated or CASP8:cFLIPL complex. These are catalytic contexts of the same enzyme, not evidence that every assembled complex necessarily produces apoptosis. |
| GO:0004197 cysteine-type endopeptidase activity | TAS Reactome:R-HSA-9013895 | ACCEPT | Summary: CASP8 catalytic activity operates in cytosolic death-regulatory complexes. Reason: The specific Reactome event describes CASP8 processing or substrate cleavage within a TLR-associated or CASP8:cFLIPL complex. These are catalytic contexts of the same enzyme, not evidence that every assembled complex necessarily produces apoptosis. |
| GO:0004197 cysteine-type endopeptidase activity | TAS Reactome:R-HSA-9697750 | ACCEPT | Summary: CASP8 catalytic activity operates in cytosolic death-regulatory complexes. Reason: The specific Reactome event describes CASP8 processing or substrate cleavage within a TLR-associated or CASP8:cFLIPL complex. These are catalytic contexts of the same enzyme, not evidence that every assembled complex necessarily produces apoptosis. |
| GO:0005123 death receptor binding | IEA GO_REF:0000107 | UNDECIDED | Summary: The direct death-receptor-binding inference remains unresolved. Reason: The rat ortholog transfer was not traced to its original assay. FADD-mediated recruitment demonstrates membership of receptor-associated complexes but does not alone establish direct CASP8 contact with a death receptor. Conversely, that canonical recruitment mechanism does not exclude other contacts. Retain the source assertion for a donor-assay audit rather than remove it. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10442631 PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TN... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The human MCF7/HeLa source reports PEA15 coprecipitation with CASP8 and competition involving FADD. Retain the association with complete-abstract access; a purified binary interface and transfer of PEA15 inhibitory activity are not established. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12198154 Caspase-10 is recruited to and activated at the native TRAIL... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected native CD95/TRAIL DISC Results and immunoprecipitation Methods support recovery of CASP8 in a FASLG-captured complex. This is ligand-containing complex association, not direct contact between extracellular FASLG and cytosolic CASP8. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12884866 Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: Prodomain-only CASP8 association with TRAF2 is reported in accessible original-paper text, but the exact P39429 construct/species mapping remains unresolved. Preserve the experimental assertion and mouse partner literally; neither relabel it as human TRAF2 nor declare a misattribution. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12884866 Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK... | MODIFY | Summary: Refine the supported interaction to its experimentally grounded binding function. Reason: Original-paper GST experiments specifically support RIPK1 binding by prodomain-only CASP8 constructs. Both DED modules are implicated; this supports protein kinase binding without assigning CASP8 kinase activity or generalizing the construct result to every intact product. Canonical cache is abstract-only; selected original text was accessed externally. Proposed replacements: protein kinase binding Supporting Evidence: PMID:12884866 only NIK and RIP, but not RICK or IKKalpha/beta, could directly bind to PDCasp8/10. |
| GO:0005515 protein binding | IPI PMID:12884866 Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The exact Q61160 mouse-FADD construct assay in the prodomain study was not independently resolved. Human FADD evidence is not a substitute for that partner mapping. Preserve the source as uncertain without relabeling the partner or claiming a species error. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12884866 Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK... | MODIFY | Summary: Refine the supported interaction to its experimentally grounded binding function. Reason: Original-paper GST experiments specifically support NIK binding by prodomain-only CASP8 constructs. This supports protein kinase binding without assigning CASP8 kinase activity or extrapolating to every intact product. Canonical cache is abstract-only; selected original text was accessed externally. Proposed replacements: protein kinase binding Supporting Evidence: PMID:12884866 could directly bind to PDCasp8/10. |
| GO:0005515 protein binding | IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The accessible primary Results place CFLAR in the later CASP8-containing TNFR signaling complex. Retain coassociation without assigning a direct interface or the same activity to all FLIP-dependent assemblies. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original study includes a separate FasL-captured Fas DISC positive control containing CASP8. Absence of CASP8 from TNFR1 complex I does not contradict this Fas association. Co-IP does not establish a direct receptor interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original FasL-captured DISC control supports CASP8 association with the ligand-containing receptor complex. The experiment does not establish direct extracellular FASLG-to-CASP8 contact. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The human TNFR study supports CASP8 and FADD coassociation in the later signaling complex. Retain the generic edge without claiming that this particular experiment resolves the isolated DED interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The human TNFR study supports RIPK1 coassociation with CASP8 in a later signaling complex. This source alone does not isolate a binary interaction or specify whether recruitment and substrate recognition use the same interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The later human TNFR signaling complex contains CASP8 and CASP10. Retain the curated coassociation without assigning a fixed heterodimer stoichiometry or transferring CASP10-specific properties to CASP8. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12888622 Caspase cleavage of tau: linking amyloid and neurofibrillary... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected recombinant assays include CASP8 cleavage of human tau with a D421E substrate control. This supports the experimentally curated enzyme-substrate association, not a stable tau complex or a complete CASP8-specific Alzheimer-disease mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:14612908 Defects in death-inducing signalling complex formation preve... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The DU145-negative study includes a positive Jurkat FADD/CASP8 co-IP control. Retain that experimental association; the title and defective cell-line context do not establish lack of binding in the positive control. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15069192 Suppression of caspase-8- and -10-associated RING proteins r... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Yeast and mammalian co-IP experiments support RNF34/CASP8 association, including E3-inactive partner constructs used to prevent loss of CASP8. No RNF34 catalytic function is transferred to CASP8 and no DED interface is inferred merely because CASP8 contains DEDs. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15509781 Calcium binding of ARC mediates regulation of caspase 8 and ... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: GST and reciprocal endogenous HEK293 co-IP experiments support calcium-sensitive binding of intact ARC/NOL3 to CASP8. Isolated ARC CARD or P/E regions do not reproduce full-length binding, so a narrower CARD-domain-binding claim is not made. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16498403 The role of receptor internalization in CD95 signaling. | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Indexed primary Results and captions directly describe CASP8 coprecipitation with human CD95 complexes in BJAB cells. Internalization perturbations distinguish recruitment contexts; no purified CASP8-receptor interface or raw-image reanalysis is claimed. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16498403 The role of receptor internalization in CD95 signaling. | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Indexed primary Results and captions describe ligand-captured CD95/CD95L complexes containing CASP8. Retain coassociation with FASLG, without inferring direct contact across the plasma membrane. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16936772 Integrin-linked kinase interacts with caspase-9 and -8 in an... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The complete abstract describes ILK overexpression, adhesion, irradiation and caspase activation in human HL60 cells, but the specific CASP8-ILK physical-interaction assay remains uninspected. The exact Q13418 partner is retained as uncertain; its name does not establish CASP8 kinase-binding or catalytic activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original monocyte-differentiation paper includes apoptotic U937 TRAIL controls supporting CASP8 association with a DR4-containing complex. Receptor-independent differentiation is a separate context. Retain coassociation rather than infer direct receptor contact. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The monocyte-differentiation source reports CFLAR in the atypical CASP8/FADD/RIP1 complex. Retain this contextual association; no unique FLIP isoform or direct interface is inferred for the unsuffixed partner. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The source reports long-FLIP association with the differentiation-associated CASP8 complex. Preserve literal O15519-1 and its experimental context without assigning a new isoform mapping or exclusive binding specificity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Positive anti-Fas apoptotic U937 controls in the differentiation paper support CASP8 association with Fas-containing complexes. Absence of receptor association during M-CSF differentiation does not negate those separate positive controls. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The differentiation source reports FADD association in the atypical CASP8 complex. Retain this contextual coassociation without interpreting it as a fixed native stoichiometry or a direct interface assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The differentiation source reports RIPK1 association and CASP8-dependent RIP1 cleavage. Retain the association while distinguishing complex recruitment from a purified binary-binding measurement. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17159907 Palmitoylation of CD95 facilitates formation of SDS-stable r... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The source describes FLIP in the high-molecular-weight CD95 DISC containing CASP8. Preserve the exact supplied FLIP isoform suffix without claiming isoform-exclusive recognition or identifying a specific interface from complex membership. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17159907 Palmitoylation of CD95 facilitates formation of SDS-stable r... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The source reports CASP8 in high-molecular-weight CD95 DISC assemblies. Retain the Fas coassociation while distinguishing receptor clustering and complex capture from direct CASP8-receptor binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17159907 Palmitoylation of CD95 facilitates formation of SDS-stable r... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: FADD and CASP8 are reported in the high-molecular-weight CD95 DISC. The abstract supports coassociation; the exact DED interface is established in other work rather than inferred from this assay alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17159907 Palmitoylation of CD95 facilitates formation of SDS-stable r... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: CASP10 and CASP8 are reported in the same high-molecular-weight DISC. Retain the association with abstract-level access, without assuming every recovered subunit contacts every other subunit directly. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17170703 A novel function of caspase-8 in the regulation of androgen-... | MODIFY | Summary: Refine the supported interaction to its experimentally grounded binding function. Reason: The human androgen-receptor study identifies CASP8 interaction motifs and substitutions that disrupt binding-related transcriptional effects. This supports nuclear androgen receptor binding without making CASP8 a receptor or asserting a new gene-regulatory process. The original cache is abstract-only. Proposed replacements: nuclear androgen receptor binding Supporting Evidence: PMID:17170703 Substitutions of the amino-acid residues critical for AR-Casp8 interactions abolished the Casp8-mediated inhibition of AR transactivation. |
| GO:0005515 protein binding | IPI PMID:17245429 FLASH links the CD95 signaling pathway to the cell nucleus a... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected Results and Methods support human FLASH association in transfected cells and endogenous human mitochondrial preparations. Viral ternary-complex experiments are distinct contexts; no constitutive human viral complex is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17245429 FLASH links the CD95 signaling pathway to the cell nucleus a... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The source supports human FLASH/CASP8 association, but donated-vector descriptions did not resolve the exact Q9WUF3 mouse-FLASH construct mapping. Preserve this separate partner row as uncertain rather than treating the human result as an exact substitute. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17479112 Ectopic expression of the serine protease inhibitor PI9 modu... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The abstract reports direct PI9/SERPINB9 association with an intermediate active CASP8 form and effects of a partner P1-site mutation. Retain contextual binding; CASP8 is the inhibited enzyme, not the serpin inhibitor. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18086677 Dynamic regulation of neutrophil survival through tyrosine p... | MODIFY | Summary: Refine the supported interaction to its experimentally grounded binding function. Reason: The source explicitly connects CASP8 Tyr310 phosphorylation with SHP1 association and dephosphorylation in neutrophil survival. This supports protein phosphatase binding; CASP8 supplies the phosphoprotein substrate and is not itself a phosphatase or phosphotyrosine-binding activity. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:18086677 facilitates its interaction with the Src-homology domain 2 containing tyrosine phosphatase-1 (SHP-1) |
| GO:0005515 protein binding | IPI PMID:18245485 Inhibition of endoplasmic reticulum stress-induced apoptosis... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The melanoma source reports exogenous and endogenous ARC/NOL3 coprecipitation with CASP8. Retain the association with abstract-level access; an isolated ARC CARD interface and antiapoptotic activity of CASP8 are not demonstrated by it. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18328427 Yes and PI3K bind CD95 to signal invasion of glioblastoma. | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The exact CASP8-Fas control in the CD95/Yes invasion paper remains uninspected. Separately read human CD95 immunoprecipitation experiments establish the same receptor-complex association. Retain the generic edge with curator deference and that independent support, without claiming source-specific invasion-complex membership was reverified. |
| GO:0005515 protein binding | IPI PMID:18485876 TNF-alpha induces two distinct caspase-8 activation pathways... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The Smac-mimetic study reports a CASP8-activating complex containing FADD. Retain the source association with abstract-level access; cycloheximide-associated signaling is a separate condition and the experiment does not isolate a binary interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18485876 TNF-alpha induces two distinct caspase-8 activation pathways... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The Smac-mimetic study reports RIPK1 association with the CASP8-activating complex. Retain this context-qualified interaction without assigning RIPK1 kinase activity to CASP8 or claiming a purified binary assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18846110 Identification of an antiapoptotic protein complex at death ... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Indexed primary Figure 7A and Methods describe DR5 immunoprecipitation recovering CASP8 in TRAIL-stimulated sensitive human MDA-MB-231 cells. Resistant cells differ. This does not place CASP8 in the unstimulated inhibitory cap or establish direct receptor contact. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19060883 ABIN-1 is a ubiquitin sensor that restricts cell death and s... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original Figure 2G caption explicitly identifies human HT1080 cells for CASP8 IP recovering A20. Retain coassociation without direct-interface or ubiquitin-sensing claims. The official corrigendum changes an author name and affiliations only. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19060883 ABIN-1 is a ubiquitin sensor that restricts cell death and s... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original human HT1080 CASP8 IP in Figure 2G recovers FADD. Retain the coassociation; the paper also contains mouse genetics, but that does not change the stated species of this experiment. The corrigendum has no biological or figure correction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19060883 ABIN-1 is a ubiquitin sensor that restricts cell death and s... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original human HT1080 CASP8 IP in Figure 2G recovers RIPK1. Retain complex association without a purified binary-binding claim. The corrigendum corrects author information only. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19427028 Cullin3-based polyubiquitination and p62-dependent aggregati... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Ligand-stimulated human H460 DR4 IP/MS identifies CASP8, with control IP and unstimulated comparisons. Retain receptor-complex association rather than a direct receptor-binding interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19427028 Cullin3-based polyubiquitination and p62-dependent aggregati... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: DISC mass spectrometry and reciprocal CASP8/CUL3 immunoprecipitation support association in the original human-cell study. CUL3-complex ubiquitin-ligase activity is not transferred to CASP8. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19524512 Receptor interacting protein kinase-3 determines cellular ne... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The exact FADD assay in the RIP3-focused source remains uninspected. Independently read target experiments establish FADD/CASP8 association, including the monocyte differentiation complex. Retain the generic edge with curator deference and independent support, while leaving the original source-specific control unverified. |
| GO:0005515 protein binding | IPI PMID:19524512 Receptor interacting protein kinase-3 determines cellular ne... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The abstract directly identifies RIPK1 in a CASP8-activating complex. Retain this partner association without inferring a purified interface or attributing the surrounding RIPK3 kinase mechanism to CASP8. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19524513 Phosphorylation-driven assembly of the RIP1-RIP3 complex reg... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Indexed original Results describe RIPK1 recruitment to CASP8 complex II in TNFR2-expressing Jurkat experiments. This is distinct from TNFR1 complex I and from RIPK3 kinase assays; retain contextual RIPK1 association. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20103630 Multivalent DR5 peptides activate the TRAIL death pathway an... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original DR5-peptide source's exact CASP8-DR4 physical-association assay or table remains uninspected. Separately read target evidence (PMID:17047155 and PMID:19427028) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:20103630 Multivalent DR5 peptides activate the TRAIL death pathway an... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original DR5-peptide source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:11717445) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:20956295 Autophagy protein microtubule-associated protein 1 light cha... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected main Results and Methods describe Fas-related DISC formation and caspase activation in human Beas-2B cells under cigarette-smoke extract and Cav-1 perturbation; the work also includes mouse experiments. Retain the curated Fas-complex association with that scope. The detailed supplementary co-IP protocol and raw blots were not inspected; do not assert direct receptor contact or unique specificity for the listed Fas isoform. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21183955 Fis1 and Bap31 bridge the mitochondria-ER interface to estab... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The complete abstract explicitly describes procaspase-8 recruitment to the Fis1-Bap31 complex and dependence on a Bap31 vDED region. This supports the curated complex association with BCAP31. Abstract access does not resolve whether that dependence maps a direct interface; do not equate vDED terminology with demonstrated direct binding to a canonical DED. The older full source PMID9334338 explicitly found no direct binding in its in-vitro test. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21458669 NEMO and RIP1 control cell fate in response to extensive DNA... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original DNA-damage source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:11717445) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:21458669 NEMO and RIP1 control cell fate in response to extensive DNA... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original DNA-damage source's exact CASP8-RIPK1 physical-association assay or table remains uninspected. Separately read target evidence (PMID:21737330) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:21525013 TWEAK induces apoptosis through a death-signaling complex co... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The complete abstract explicitly reports TNFR1-dependent RIP1-FADD-caspase-8 complex assembly and loss of FADD-caspase-8 association after RIP1 knockdown. It also says FADD and caspase-8 do not join the proximal FN14 complex. Retain qualified coassociation for both partners, not direct binary contact or membership in the primary TWEAK-FN14 complex. PMC access was challenged; no full Methods claim is made. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21525013 TWEAK induces apoptosis through a death-signaling complex co... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The complete abstract explicitly reports TNFR1-dependent RIP1-FADD-caspase-8 complex assembly and loss of FADD-caspase-8 association after RIP1 knockdown. It also says FADD and caspase-8 do not join the proximal FN14 complex. Retain qualified coassociation for both partners, not direct binary contact or membership in the primary TWEAK-FN14 complex. PMC access was challenged; no full Methods claim is made. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21625644 Modulation of the CD95-induced apoptosis: the role of CD95 N... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected Results, captions and Methods directly describe caspase-8 recovery and processing in anti-CD95 DISC preparations in human cell systems, including HeLa, SKW6.4 and Hut78. Glycosylation mutants, receptor-expression checks and control conditions constrain the interpretation. Retain Fas-complex association; the pull-down does not establish a direct CASP8-receptor interface. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21713032 The naturally processed CD95L elicits a c-yes/calcium/PI3K-d... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected Results and Methods distinguish cl-CD95L-induced MISC, which lacks caspase-8, from the APO1-3-induced apoptotic DISC positive control that contains it in human H9 cells and activated peripheral lymphocytes. Retain the latter Fas association, not a role for CASP8 in the migratory MISC. The 2019 and 2023 corrections were read, including the corrected Figure 5C control caption; they are explicitly recorded below. Listed Fas isoform identity is preserved without a uniqueness claim. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original DJ-1/TRAIL source's exact CASP8-DR4 physical-association assay or table remains uninspected. Separately read target evidence (PMID:17047155) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | MODIFY | Summary: Refine the supported interaction to its experimentally grounded binding function. Reason: The complete cached and official publisher abstracts explicitly place competition between DJ-1 and procaspase-8 at the FADD death effector domain. This supports refinement of the FADD row to the already-existing GO:0035877 activity, with abstract-level access stated. The publisher full body remains subscription-only. The same abstract does not resolve the exact DR4 coassociation row; it cannot be rejected from the general TRAIL wording. Proposed replacements: death effector domain binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21803845 PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis t... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original PMLRARalpha source's exact CASP8-Fas physical-association assay or table remains uninspected. Separately read target evidence (PMID:16498403) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original liver-network source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:11717445) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:22173242 RIP1 is required for IAP inhibitor-mediated sensitization of... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The complete abstract explicitly identifies a RIP1-FADD-caspase-8 complex in childhood ALL cells after IAP inhibitor plus AraC treatment; RIP1 knockdown, kinase inhibition and TNF blockade suppress complex formation or interaction. Retain context-qualified association with each partner. Full Methods and direct-interface evidence were not read; do not generalize a co-complex result into a specific binary binding mode. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22173242 RIP1 is required for IAP inhibitor-mediated sensitization of... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The complete abstract explicitly identifies a RIP1-FADD-caspase-8 complex in childhood ALL cells after IAP inhibitor plus AraC treatment; RIP1 knockdown, kinase inhibition and TNF blockade suppress complex formation or interaction. Retain context-qualified association with each partner. Full Methods and direct-interface evidence were not read; do not generalize a co-complex result into a specific binary binding mode. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22267217 Dectin-1 is an extracellular pathogen sensor for the inducti... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The complete abstract explicitly describes recruitment of MALT1-caspase-8 and ASC to the CARD9-BCL10-MALT1 scaffold in dendritic-cell signaling. Retain qualified MALT1 association while deferring to the experimental curator. The abstract does not state the species or establish a mapped MALT1 domain interface; do not assign a CARD-domain interaction to CASP8 or infer direct MALT1-protease binding from membership alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22274400 Pick your poison: the Ripoptosome, a cell death platform reg... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original ripoptosome follow-up source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:21737330) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:22274400 Pick your poison: the Ripoptosome, a cell death platform reg... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original ripoptosome follow-up source's exact CASP8-RIPK1 physical-association assay or table remains uninspected. Separately read target evidence (PMID:21737330) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:23955153 Pathogen blocks host death receptor signalling by arginine G... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original bacterial NleB source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:11717445) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:23955153 Pathogen blocks host death receptor signalling by arginine G... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original bacterial NleB source's exact CASP8-RIPK1 physical-association assay or table remains uninspected. Separately read target evidence (PMID:21737330) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:24025841 A type III effector antagonizes death receptor signalling du... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected Results and Methods use Fc-tagged Fas ligand and protein G to recover the Fas DISC from HeLa cells. This supports association of CASP8 with a ligand-containing receptor complex. It does not establish direct binding between the extracellular ligand and the intracellular protease. Retain qualified non-core association rather than inventing ligand-binding or receptor activity for CASP8. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24438025 Involvement of caspase 8 and c-FLIPL in the proangiogenic ef... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original angiogenesis source's exact CASP8-CFLAR physical-association assay or table remains uninspected. Separately read target evidence (PMID:17047155 and PMID:38710704) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:25043603 Apo2L/TRAIL and the death receptor 5 agonist antibody AMG 65... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original DR5-antibody source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:11717445) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:25890358 TNFΞ± sensitizes neuroblastoma cells to FasL-, cisplatin- and... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected Results, the relevant figure caption and Methods show Fc:hFasL-dependent recovery of FADD and caspase-8 from TNF-pretreated human SK-N-AS cells, with unstimulated or untreated comparisons. This supports ligand-containing DISC coassociation, not a purified FASLG-CASP8 binary interaction. Preserve the partner while qualifying the assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25911380 The seventh zinc finger motif of A20 is required for the sup... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original A20 source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:19060883) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:25911380 The seventh zinc finger motif of A20 is required for the sup... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original A20 source's exact CASP8-RIPK1 physical-association assay or table remains uninspected. Separately read target evidence (PMID:19060883) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:26942442 An Evolution-Guided Analysis Reveals a Multi-Signaling Regul... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected Results, the complete Figure 2 caption and Methods describe anti-Fas isolation of signaling complexes from human SW480 cells expressing wild-type or mutant Fas-V5, with caspase-8 recruitment/processing and ligand-control comparisons. Retain Fas-complex association. Preserve P25445-1 exactly without claiming an isoform-exclusive biological interaction or a direct CASP8-Fas contact. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-ΞΊB s... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original Virotrap source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:11717445) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original kinase-network source's exact CASP8-RIPK1 physical-association assay or table remains uninspected. Separately read target evidence (PMID:12884866 and PMID:21737330) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The complete abstract describes a modified yeast-two-hybrid interaction network. The six exact target pairs and isoform constructs were not retrieved from the primary table. UniProt repeats all six exact accessions, but those database records can share IntAct provenance and are not an independent experiment. Preserve RAF1, APP, UNG-2, PLK1, FMR1-7 and VPS33A separately; do not infer kinase binding, DNA repair, APP processing or RNA regulation from their names. These exact novel or isoform-qualified pairs lack separately verified target evidence in this review, so the original assertions remain uncertain rather than removed. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The complete abstract describes a modified yeast-two-hybrid interaction network. The six exact target pairs and isoform constructs were not retrieved from the primary table. UniProt repeats all six exact accessions, but those database records can share IntAct provenance and are not an independent experiment. Preserve RAF1, APP, UNG-2, PLK1, FMR1-7 and VPS33A separately; do not infer kinase binding, DNA repair, APP processing or RNA regulation from their names. These exact novel or isoform-qualified pairs lack separately verified target evidence in this review, so the original assertions remain uncertain rather than removed. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The complete abstract describes a modified yeast-two-hybrid interaction network. The six exact target pairs and isoform constructs were not retrieved from the primary table. UniProt repeats all six exact accessions, but those database records can share IntAct provenance and are not an independent experiment. Preserve RAF1, APP, UNG-2, PLK1, FMR1-7 and VPS33A separately; do not infer kinase binding, DNA repair, APP processing or RNA regulation from their names. These exact novel or isoform-qualified pairs lack separately verified target evidence in this review, so the original assertions remain uncertain rather than removed. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The complete abstract describes a modified yeast-two-hybrid interaction network. The six exact target pairs and isoform constructs were not retrieved from the primary table. UniProt repeats all six exact accessions, but those database records can share IntAct provenance and are not an independent experiment. Preserve RAF1, APP, UNG-2, PLK1, FMR1-7 and VPS33A separately; do not infer kinase binding, DNA repair, APP processing or RNA regulation from their names. These exact novel or isoform-qualified pairs lack separately verified target evidence in this review, so the original assertions remain uncertain rather than removed. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The complete abstract describes a modified yeast-two-hybrid interaction network. The six exact target pairs and isoform constructs were not retrieved from the primary table. UniProt repeats all six exact accessions, but those database records can share IntAct provenance and are not an independent experiment. Preserve RAF1, APP, UNG-2, PLK1, FMR1-7 and VPS33A separately; do not infer kinase binding, DNA repair, APP processing or RNA regulation from their names. These exact novel or isoform-qualified pairs lack separately verified target evidence in this review, so the original assertions remain uncertain rather than removed. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The complete abstract describes a modified yeast-two-hybrid interaction network. The six exact target pairs and isoform constructs were not retrieved from the primary table. UniProt repeats all six exact accessions, but those database records can share IntAct provenance and are not an independent experiment. Preserve RAF1, APP, UNG-2, PLK1, FMR1-7 and VPS33A separately; do not infer kinase binding, DNA repair, APP processing or RNA regulation from their names. These exact novel or isoform-qualified pairs lack separately verified target evidence in this review, so the original assertions remain uncertain rather than removed. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original BioPlex source's exact CASP8-DR4 physical-association assay or table remains uninspected. Separately read target evidence (PMID:19427028) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original BioPlex source's exact CASP8-CFLAR physical-association assay or table remains uninspected. Separately read target evidence (PMID:17047155) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original BioPlex source's exact CASP8-Fas physical-association assay or table remains uninspected. Separately read target evidence (PMID:16498403) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original BioPlex source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:11717445) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The cache full-text flag is true but the extracted HTML is short and incomplete. This breast-cancer interaction study includes genotype/context dependence; the exact CASP8-FADD edge and wild-type versus mutant bait provenance were not read. A generic FADD mechanism must not be presented as validation of this specific experimental construct. The unresolved wild-type-versus-mutant bait context is material, so evidence for ordinary FADD recruitment is not used to erase this source-specific uncertainty. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9208847 Casper is a FADD- and caspase-related inducer of apoptosis. | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The complete abstract explicitly states that Casper/CFLAR interacts with CASP8. Retain the original generic association with abstract-level access and curator deference. The precise CFLAR-binding interface is not mapped by the accessible excerpt. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9208847 Casper is a FADD- and caspase-related inducer of apoptosis. | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The complete source abstract describes FADD-mediated CASP8 recruitment through death-effector domains. Retain the original generic FADD association; the separate existing DED annotation captures the independently supported narrower mechanism without altering this source object. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9334338 p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated prote... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected full Methods/Results/Discussion describe tagged human BCAP31 and caspase-8 coimmunoprecipitation, specificity comparisons including Bax, and BCAP31 cleavage. Crucially, the authors did not detect direct BCAP31-caspase-8 binding in vitro and proposed an unidentified bridging factor. Retain qualified coassociation; do not convert weak sequence resemblance or substrate cleavage into proof of direct DED binding. The direct-negative assay does not negate the cellular co-IP. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9343261 Bovine herpesvirus 4 BORFE2 protein inhibits Fas- and tumor ... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: The original viral BORFE2 source's exact CASP8-FADD physical-association assay or table remains uninspected. Separately read target evidence (PMID:11717445) establishes association with this same literal partner. Retain the generic edge with experimental-curator deference and independent corroboration; this does not authenticate the original construct, dataset entry or stimulus-specific mechanism. No direct interface or finer partner-derived activity is inferred. |
| GO:0005515 protein binding | IPI PMID:9343261 Bovine herpesvirus 4 BORFE2 protein inhibits Fas- and tumor ... | UNDECIDED | Summary: The exact source-specific interaction remains unresolved. Reason: The complete official abstract explicitly reports yeast-two-hybrid binding of bovine-herpesvirus BORFE2 to the caspase-8 prodomain; FADD appears in the background mechanism. The primary PDF/construct details were not obtained. An official current Q1XBR6 accession-to-BORFE2 mapping was also not obtained, so the exact viral identifier and host construct remain unresolved. Preserve that uncertainty, not a wrong-species or wrong-gene allegation. The viral partner is not a normal human core function. The viral accession is preserved literally; no replacement identifier or human endogenous role is asserted. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9560245 ARC, an inhibitor of apoptosis expressed in skeletal muscle ... | KEEP AS NON CORE | Summary: Retain the supported association as a contextual CASP8 interaction. Reason: Selected full Methods and Results show ARC/NOL3 co-IP with human CASP8, specificity comparisons against other caspases, and interaction with the CASP8 N-terminal 1-215 fragment but not residues 216-496; catalytic C377S and empty-vector controls constrain activity experiments. This supports qualified ARC association. CASP8 using its own DED-containing region does not imply that its partner supplies a DED, and the NOL3 CARD was not independently mapped as the binding surface here. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain context-dependent nuclear CASP8 localization. Reason: The original ortholog and UniProt location sources are preserved. Nuclear trafficking contexts are compatible with the CASP8/FLASH literature and curated UniProt localization, but do not replace the better-established cytosolic catalytic pool or demonstrate that every CASP8 product is constitutively nuclear. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain context-dependent nuclear CASP8 localization. Reason: The original ortholog and UniProt location sources are preserved. Nuclear trafficking contexts are compatible with the CASP8/FLASH literature and curated UniProt localization, but do not replace the better-established cytosolic catalytic pool or demonstrate that every CASP8 product is constitutively nuclear. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: CASP8 has a cytoplasmic pool relevant to its core functions. Reason: Direct target localization and cytosolic recruitment/processing evidence support the broad cytoplasm assertion. The IBA or ortholog mappings are not rejected because their source lists contain diverse caspases; no independent ancestral-node inspection or isoform-wide localization claim is made. |
| GO:0005737 cytoplasm | IDA PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | ACCEPT | Summary: Retain the experimentally curated cytoplasmic localization. Reason: The Hsp70/GATA1 abstract does not expose the CASP8 localization experiment. Independent target-specific microscopy and fractionation in the plectin study substantiate a cytoplasmic CASP8 pool. Acceptance relies on that corroboration and curator deference, not an inferred error from the paper title. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: CASP8 has a cytoplasmic pool relevant to its core functions. Reason: Direct target localization and cytosolic recruitment/processing evidence support the broad cytoplasm assertion. The IBA or ortholog mappings are not rejected because their source lists contain diverse caspases; no independent ancestral-node inspection or isoform-wide localization claim is made. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: CASP8 has a cytoplasmic pool relevant to its core functions. Reason: Direct target localization and cytosolic recruitment/processing evidence support the broad cytoplasm assertion. The IBA or ortholog mappings are not rejected because their source lists contain diverse caspases; no independent ancestral-node inspection or isoform-wide localization claim is made. |
| GO:0005739 mitochondrion | TAS PMID:10891503 Identification of the cytolinker plectin as a major early in... | KEEP AS NON CORE | Summary: CASP8 localization includes a context-dependent mitochondrial pool. Reason: Subunit-specific antibodies, microscopy, fractionation and mitochondrial-binding experiments support endogenous CASP8 localization in the studied human cells. Active subunits redistribute during apoptosis while the prodomain remains differently distributed. These observations do not make mitochondria the universal CASP8 activation site. Supporting Evidence: |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-351863 | KEEP AS NON CORE | Summary: Retain the curated mitochondrial outer-membrane context. Reason: Reactome places active CASP8 at the mitochondrial surface in these events. The plectin paper independently supports mitochondrial association, while its precise loose outer-membrane-attachment discussion includes evidence not fully presented there. BAP31 cleavage at the ER does not itself relocate CASP8 into the ER membrane. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-351894 | KEEP AS NON CORE | Summary: Retain the curated mitochondrial outer-membrane context. Reason: Reactome places active CASP8 at the mitochondrial surface in these events. The plectin paper independently supports mitochondrial association, while its precise loose outer-membrane-attachment discussion includes evidence not fully presented there. BAP31 cleavage at the ER does not itself relocate CASP8 into the ER membrane. |
| GO:0005829 cytosol | IDA PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | ACCEPT | Summary: CASP8 has an independently supported cytosolic pool. Reason: The original Hsp70-paper CASP8 localization control remains uninspected, but the target-specific FLICE activation source and cytosolic CASP8-containing complexes corroborate this same compartment. This is cross-source support and experimental-curator deference, not a claim to have re-read the original localization assay. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: The cytosolic ortholog transfer is corroborated on human CASP8. Reason: CASP8 is recruited from the cytosolic pool and functions in cytosolic processing and RIPK1-regulatory complexes. The rat source record remains exact; its individual localization assay has not been independently reconstructed. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-139898 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in BID cleavage. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-139952 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in CASP8 processing and release. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141156 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TRAIL-associated procaspase dimerization. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141159 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TNF-associated procaspase dimerization. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201637 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in plectin cleavage. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2562541 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TLR4-associated ripoptosome assembly. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2562564 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TLR4-associated CASP8 processing. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2672196 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in viral serpin inhibition. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3371359 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TRAIL-associated CASP8/cFLIPL assembly. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3371360 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TNF-associated CASP8/cFLIPL assembly. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3465429 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in cFLIPS association. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3465448 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in DISC-associated CASP8/cFLIPL processing. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3465459 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in FAS-associated CASP8/cFLIPL assembly. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-350319 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in the broader vimentin-cleavage pathway. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. The summary assigns the vimentin cut to CASP6; CASP8 cytosol is corroborated independently, not by claiming it makes that cut. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351863 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in translocation from cytosol to mitochondria. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5357828 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in RIPK1 cleavage. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5634228 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TRAF1 cleavage. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5660662 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in ASC-associated complex formation. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5660663 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in pro-IL1B cleavage. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5660665 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in MALT1-associated recruitment. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5675456 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in CASP8/cFLIPL heterodimerization. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5692550 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in viral UL36 inhibition. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-622420 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in NOD1-associated death signaling. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-73945 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in FAS-associated dimerization. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75146 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TRAIL/FADD-associated recruitment. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75240 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in cytosolic TNFR complex-II recruitment. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-83586 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in FAS/FADD-associated recruitment. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013889 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TLR3-associated ripoptosome assembly. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013895 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TLR3-associated CASP8 processing. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933523 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in CASP8/CASP10 assembly. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933526 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in FADD-associated recruitment. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933532 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in caspase processing. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-933539 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in IKK recruitment. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. The source describes the detailed IKK-recruitment mechanism as proposed. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9686930 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in RIPK3 cleavage. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9687458 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in viral HSV1 RIR1 binding. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. The viral partner carries its own RHIM; no CASP8 RHIM activity is inferred. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9693929 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in cleavage-resistant RIPK1 signaling. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9697747 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in TNFR-associated CASP8/cFLIPL processing. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. The summary contains imprecise FLIP nomenclature; CFLAR is not a CASP8 splice product. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9697750 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in RIPK1 cleavage by CASP8/cFLIPL. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9757951 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in N4BP1 cleavage. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823816 | ACCEPT | Summary: Cytosol is a supported core CASP8 compartment. Reason: The cached event places CASP8 in OPTN association. Cytosol is a central compartment for the target enzyme and recruitment functions, so the compartment itself is accepted even when the particular event is contextual. No activity of another event participant is transferred to CASP8. |
| GO:0005856 cytoskeleton | TAS PMID:10891503 Identification of the cytolinker plectin as a major early in... | KEEP AS NON CORE | Summary: Active CASP8 associates with the cytoskeleton during death-receptor apoptosis. Reason: The human-cell microscopy and fractionation distinguish active subunits from prodomain localization and identify plectin as a directly cleaved substrate. This is a regulated pool, not a claim that CASP8 is itself a constitutive structural cytoskeletal protein. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain regulated plasma-membrane association. Reason: Target imaging places CASP8 at leading lamellae and membrane ruffles, including catalytically inactive constructs, and receptor-associated recruitment provides another membrane-proximal context. Restricting the broad membrane assertion to lamellipodia would exclude other supported contexts. No transmembrane topology is implied. |
| GO:0006508 proteolysis | IDA PMID:12888622 Caspase cleavage of tau: linking amyloid and neurofibrillary... | ACCEPT | Summary: Tau cleavage is a contextual CASP8 proteolytic reaction. Reason: Selected recombinant assays include CASP8 cleavage of human tau with cleavage-site and enzyme controls. This is a direct instance of its core proteolytic process, without assigning every tau cleavage or the complete Alzheimer-disease pathway to CASP8. Supporting Evidence: |
| GO:0006508 proteolysis | IEA GO_REF:0000120 | ACCEPT | Summary: Proteolysis captures the enzyme work performed by CASP8. Reason: This broad electronic process term is supported by direct CASP8 cleavage of multiple protein substrates. It is a legitimate parent process of the more specific proteolytic pathways, not a false assertion simply because more informative descendants exist. |
| GO:0006915 apoptotic process | IBA GO_REF:0000033 | ACCEPT | Summary: CASP8 directly participates in apoptosis. Reason: Proteolytic activation of effector caspases and physical recruitment into death complexes support the broad apoptotic-process assertion. Replacing every broad row by the death-domain-receptor branch would be too restrictive for TLR and other cytosolic activation contexts. The IBA is retained without claiming an independently inspected PTN placement. |
| GO:0006915 apoptotic process | IEA GO_REF:0000002 | ACCEPT | Summary: CASP8 directly participates in apoptosis. Reason: The CASP8-family InterPro mapping is supported by proteolytic activation of effector caspases. The broad apoptotic-process term also accommodates non-death-receptor activation contexts and should not be replaced wholesale by a single receptor-specific branch. |
| GO:0006915 apoptotic process | IMP PMID:22891283 Vesicles released by activated T cells induce both Fas-media... | ACCEPT | Summary: Retain CASP8 participation in the experimentally curated apoptotic context. Reason: The source distinguishes FAS/RIP-dependent apoptosis from a second nonapoptotic vesicle-induced outcome. Its full CASP8-specific controls remain unavailable, but target participation in apoptosis is directly established elsewhere. No claim that all vesicle-induced death requires CASP8 is made. |
| GO:0007507 heart development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the curated developmental context with a donor-access limit. Reason: This existing mouse-to-human ISS assertion concerns heart development, not an additional molecular activity. The original mouse developmental assay was not independently reconstructed, so the precise cell type and catalytic versus survival-checkpoint mechanism remain unresolved. The reviewed target record supports an essential developmental context; absence of a human embryonic experiment is not a contradiction. Supporting Evidence: file:human/CASP8/CASP8-uniprot.txt |
| GO:0008233 peptidase activity | IDA PMID:19740745 A truncated form of p23 down-regulates telomerase activity v... | MODIFY | Summary: Refine the curated peptidase activity to cysteine endopeptidase activity. Reason: The abstract reports p23 processing but does not expose every CASP8-specific enzyme control. Independent direct CASP8 cleavage evidence supports the more precise existing molecular-function term. This retains the experimental assertion with an explicit access limit rather than treating the abstract omission as evidence against proteolysis. Proposed replacements: cysteine-type endopeptidase activity |
| GO:0008233 peptidase activity | IEA GO_REF:0000107 | MODIFY | Summary: Refine broad peptidase activity to cysteine-type endopeptidase activity. Reason: CASP8 catalyzes internal peptide-bond cleavage after aspartate. Its measured proteolysis and curated specificity support the existing narrower endopeptidase term; the original donor/domain assertion remains intact. This refinement does not imply that the short catalytic-domain-deficient products retain enzymatic activity. Proposed replacements: cysteine-type endopeptidase activity |
| GO:0008233 peptidase activity | IMP PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | MODIFY | Summary: The monocyte source supports CASP8 protease activity; refine its specificity. Reason: The primary abstract and accessible indexed text explicitly identify CASP8 at the head of a proteolytic cascade, with RIP1 cleavage and macrophage differentiation in peripheral-blood monocytes. This is enzyme work, not only a differentiation phenotype. Refine peptidase to cysteine-type endopeptidase without claiming the canonical cache contains the complete paper. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:17047155 caspase-8 cleaves RIP1, which prevents sustained NF-kappaB activation |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine broad peptidase activity to cysteine-type endopeptidase activity. Reason: CASP8 catalyzes internal peptide-bond cleavage after aspartate. Its measured proteolysis and curated specificity support the existing narrower endopeptidase term; the original donor/domain assertion remains intact. This refinement does not imply that the short catalytic-domain-deficient products retain enzymatic activity. Proposed replacements: cysteine-type endopeptidase activity |
| GO:0008234 cysteine-type peptidase activity | TAS PMID:8681376 Involvement of MACH, a novel MORT1/FADD-interacting protease... | MODIFY | Summary: Refine broad peptidase activity to cysteine-type endopeptidase activity. Reason: CASP8 catalyzes internal peptide-bond cleavage after aspartate. Its measured proteolysis and curated specificity support the existing narrower endopeptidase term; the original donor/domain assertion remains intact. This refinement does not imply that the short catalytic-domain-deficient products retain enzymatic activity. Proposed replacements: cysteine-type endopeptidase activity |
| GO:0008303 caspase complex | IPI PMID:38710704 Deciphering DED assembly mechanisms in FADD-procaspase-8-cFL... | ACCEPT | Summary: CASP8 forms caspase-containing activation complexes. Reason: Reconstituted DED assemblies and cell-based interface tests support complex membership. Engineered self-association and catalytic-site mutants facilitated structural analysis; the reported stoichiometries must not be treated as invariant native DISC composition. Supporting Evidence: |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IBA GO_REF:0000033 | ACCEPT | Summary: CASP8 is a direct effector of death-domain receptor apoptotic signaling. Reason: FADD-associated recruitment, CASP8 processing and downstream caspase activation establish the pathway. The IBA target appearing in its own descendant-evidence list is legitimate support, not circularity. Catalytically incomplete splice products can modulate rather than execute the reaction. |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IDA PMID:9184224 FLICE is activated by association with the CD95 death-induci... | ACCEPT | Summary: CASP8 is a direct effector of death-domain receptor apoptotic signaling. Reason: The target FLICE study directly describes DISC-associated recruitment, processing and downstream apoptotic signaling. Catalytically incomplete splice products can modulate rather than execute the reaction. |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IEA GO_REF:0000117 | ACCEPT | Summary: CASP8 is a direct effector of death-domain receptor apoptotic signaling. Reason: The ARBA assertion agrees with independently established human DISC recruitment, CASP8 processing and downstream apoptotic signaling. This does not assign the same enzymatic capacity to catalytic-domain-deficient products. |
| GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process | IEA GO_REF:0000107 | MODIFY | Summary: CASP8 activates apoptotic endopeptidases by cleavage. Reason: GO:0140608 cysteine-type endopeptidase activator activity is defined as "Binds to and increases the activity of a cysteine-type endopeptidase", with no restriction to non-proteolytic activators, so an initiator caspase that binds and cleaves effector procaspases to activate them fits the genus as well as it fitted the precomposed term. Earlier reasoning: The official GO:0008656 comment expressly includes active caspases that cleave inactive effector caspases. Primary procaspase-7 assays directly demonstrate this CASP8 activity. Proteolytic chemistry is therefore compatible with this activator term; the previous nonproteolytic-only interpretation was incorrect. This is part of the same protease mechanism, not a separate new catalytic activity. Proposed replacements: cysteine-type endopeptidase activator activity Context of precomposed term: module death_receptor_apoptotic_signaling / casp8_caspase_8_initiator_protease in core functions Decomposed from the precomposed GO:0008656 (projects/INVOLVED_IN_PRECOMPOSITION.md) to its genus GO:0140608; the apoptotic context is carried by the module element and by the core function on cysteine-type endopeptidase activity in extrinsic apoptotic signaling, of which activating effector caspases is an output (the core function names the protease activity, not GO:0140608 itself). Supporting Evidence: |
| GO:0009967 positive regulation of signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CASP8 can positively regulate signaling in defined contexts. Reason: Prodomain-dependent NF-kappaB activation and receptor-associated caspase activation support this broad regulatory term. Breadth alone is not evidence of an erroneous ARBA annotation. The direction and catalytic requirement vary between complexes and constructs. |
| GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway | TAS Reactome:R-HSA-5357905 | KEEP AS NON CORE | Summary: CASP8 regulates TNF signaling through context-dependent complex and substrate effects. Reason: The Reactome overview is supported by RIPK1 cleavage and CASP8/cFLIP complexes. Human cleavage-resistant RIPK1 variants demonstrate why this regulation cannot be reduced to universal promotion of apoptosis or universal suppression of TNF responses. |
| GO:0016485 protein processing | IEA GO_REF:0000120 | ACCEPT | Summary: CASP8 performs limited proteolytic protein processing. Reason: Autoprocessing and cleavage of procaspase and gasdermin substrates directly support the broad existing process assertion. It is not a substrate-only participation inference: CASP8 catalyzes the relevant cuts. |
| GO:0030027 lamellipodium | IDA PMID:18216014 Identification of a critical tyrosine residue in caspase 8 t... | KEEP AS NON CORE | Summary: CASP8 is recruited to lamellipodia in migration assays. Reason: Human neuroblastoma reconstitution and imaging support leading-lamella/ruffle association. Catalytically inactive CASP8 and domain constructs separate this pool from apoptotic enzyme activity; the observation does not imply constitutive localization in every cell type. Supporting Evidence: |
| GO:0030027 lamellipodium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CASP8 is recruited to lamellipodia in migration assays. Reason: Human neuroblastoma reconstitution and imaging support leading-lamella/ruffle association. Catalytically inactive CASP8 and domain constructs separate this pool from apoptotic enzyme activity; the observation does not imply constitutive localization in every cell type. Supporting Evidence: |
| GO:0030101 natural killer cell activation | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | KEEP AS NON CORE | Summary: Human CASP8 deficiency supports this lymphocyte-activation context. Reason: The original review cache is abstract-only and does not expose this specific section. Independent primary human genetics explicitly documents defects in T-, B- and NK-cell activation in CASP8 deficiency, supporting these existing annotations. Clinical loss of function does not by itself specify the direct molecular step or justify an additional activation core. |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CASP8 contributes to differentiation in defined cell contexts. Reason: The peripheral-blood monocyte study links CASP8 proteolysis and RIP1/NF-kappaB control to macrophage differentiation. This supports the existing broad electronic differentiation assertion without transferring the result to every lineage. Supporting Evidence: |
| GO:0030163 protein catabolic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CASP8 substrate cleavage supports the protein-breakdown context. Reason: RIP1 cleavage and processing of other protein substrates support the existing annotations. Limited cleavage often activates or remodels a substrate rather than completely degrading it, so these rows do not imply that CASP8 is a general protein-disposal system. The original mouse donor assay is not independently reconstructed. |
| GO:0030163 protein catabolic process | IMP PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts... | KEEP AS NON CORE | Summary: CASP8 substrate cleavage supports the protein-breakdown context. Reason: The target source identifies CASP8 cleavage of RIP1 during TNF signaling. This supports the curated protein-breakdown context, although limited cleavage can remodel a substrate rather than completely degrade it. The short abstract-like cache does not expose the complete original controls. Supporting Evidence: PMID:10521396 the death domain kinase RIP, a key component of the TNF signaling complex, was cleaved by Caspase-8 |
| GO:0030163 protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CASP8 substrate cleavage supports the protein-breakdown context. Reason: RIP1 cleavage and processing of other protein substrates support the existing annotations. Limited cleavage often activates or remodels a substrate rather than completely degrading it, so these rows do not imply that CASP8 is a general protein-disposal system. The original mouse donor assay is not independently reconstructed. |
| GO:0030225 macrophage differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CASP8 proteolysis contributes to macrophage differentiation. Reason: The human monocyte source identifies CASP8 activation, RIP1 cleavage and limitation of sustained NF-kappaB signaling during M-CSF-driven differentiation. It independently corroborates the review/phylogenetic assertions. The exact PAINT ancestral node remains uninspected; no inference is made from donor-list size. |
| GO:0030225 macrophage differentiation | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | KEEP AS NON CORE | Summary: CASP8 proteolysis contributes to macrophage differentiation. Reason: The original review cache is abstract-only, but the independent human monocyte source links CASP8 activation, RIP1 cleavage and limitation of sustained NF-kappaB signaling to M-CSF-driven macrophage differentiation. This corroborates the existing TAS assertion without claiming that its full review section was read. |
| GO:0030335 positive regulation of cell migration | IDA PMID:18216014 Identification of a critical tyrosine residue in caspase 8 t... | KEEP AS NON CORE | Summary: CASP8 promotes migration through a separable nonapoptotic mechanism. Reason: Human-cell reconstitution, wound migration and localization assays distinguish catalytic-domain recruitment and Y380-dependent signaling from protease activity. Catalytically inactive CASP8 retains relevant behavior. These experiments do not establish a universal migration effect in all human cells. Supporting Evidence: |
| GO:0030690 Noc1p-Noc2p complex | IEA GO_REF:0000107 | UNDECIDED | Summary: CASP8 membership in an analogous preribosomal Noc complex remains unverified. Reason: The current official term specifies a heterodimer associated with 90S and 66S preribosomes and permits analogous complexes in other eukaryotes, as documented in the quoted ontology comment. The mouse Casp8 donor O89110 is explicitly linked by the historical MGI annotation graph to IMP evidence from PMID:14657025. Its canonical cache is abstract-only; separately inspected Results, Figure 6 and selected Methods describe NDG1-triggered CASP8 processing and activity in 293T cells, rather than a demonstrated preribosomal heterodimer. These passages do not establish complex membership, but the original curator evidence mapping and uninspected material remain unresolved. Retain UNDECIDED specifically for that membership/source-mapping question, without accepting the electronic inference, asserting absence in every species, or treating the yeast-derived name as a taxon exclusion. The ontology citation supports term scope; the paper citation identifies the donor-evidence audit, not positive complex membership. Supporting Evidence: GO:0030690 the term nevertheless can be used for analogous complexes in other eukaryotes |
| GO:0031264 death-inducing signaling complex | IDA PMID:11101870 Fas triggers an alternative, caspase-8-independent cell deat... | ACCEPT | Summary: CASP8 membership of FADD-associated DISC assemblies is established. Reason: The original experimental or ortholog source is retained. Human CASP8 recruitment and processing at the CD95 DISC independently substantiate the complex assignment; PMID:11717445 explicitly assays CASP8 alongside CASP10. The full controls of the RIP-dependent alternative-death and PMLRARalpha papers remain incompletely accessible. Their titles do not establish a target-misattribution error. |
| GO:0031264 death-inducing signaling complex | IDA PMID:21803845 PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis t... | ACCEPT | Summary: CASP8 membership of FADD-associated DISC assemblies is established. Reason: The original experimental or ortholog source is retained. Human CASP8 recruitment and processing at the CD95 DISC independently substantiate the complex assignment; PMID:11717445 explicitly assays CASP8 alongside CASP10. The full controls of the RIP-dependent alternative-death and PMLRARalpha papers remain incompletely accessible. Their titles do not establish a target-misattribution error. |
| GO:0031264 death-inducing signaling complex | IEA GO_REF:0000107 | ACCEPT | Summary: CASP8 membership of FADD-associated DISC assemblies is established. Reason: The original experimental or ortholog source is retained. Human CASP8 recruitment and processing at the CD95 DISC independently substantiate the complex assignment; PMID:11717445 explicitly assays CASP8 alongside CASP10. The full controls of the RIP-dependent alternative-death and PMLRARalpha papers remain incompletely accessible. Their titles do not establish a target-misattribution error. |
| GO:0031265 CD95 death-inducing signaling complex | IBA GO_REF:0000033 | ACCEPT | Summary: CASP8 membership of FADD-associated DISC assemblies is established. Reason: The original experimental or ortholog source is retained. Human CASP8 recruitment and processing at the CD95 DISC independently substantiate the complex assignment; PMID:11717445 explicitly assays CASP8 alongside CASP10. The full controls of the RIP-dependent alternative-death and PMLRARalpha papers remain incompletely accessible. Their titles do not establish a target-misattribution error. |
| GO:0031265 CD95 death-inducing signaling complex | IDA PMID:11717445 Caspase-10 is an initiator caspase in death receptor signali... | ACCEPT | Summary: CASP8 membership of FADD-associated DISC assemblies is established. Reason: The original experimental or ortholog source is retained. Human CASP8 recruitment and processing at the CD95 DISC independently substantiate the complex assignment; PMID:11717445 explicitly assays CASP8 alongside CASP10. The full controls of the RIP-dependent alternative-death and PMLRARalpha papers remain incompletely accessible. Their titles do not establish a target-misattribution error. |
| GO:0031265 CD95 death-inducing signaling complex | IEA GO_REF:0000107 | ACCEPT | Summary: CASP8 membership of FADD-associated DISC assemblies is established. Reason: The original experimental or ortholog source is retained. Human CASP8 recruitment and processing at the CD95 DISC independently substantiate the complex assignment; PMID:11717445 explicitly assays CASP8 alongside CASP10. The full controls of the RIP-dependent alternative-death and PMLRARalpha papers remain incompletely accessible. Their titles do not establish a target-misattribution error. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:15069192 Suppression of caspase-8- and -10-associated RING proteins r... | KEEP AS NON CORE | Summary: Retain CASP8 association with the specified ubiquitin ligase. Reason: The CARP study supports interaction with and regulation of caspase-8/10 by RING proteins. This is binding to a ligase, not CASP8 ubiquitin-ligase catalytic activity. The exact Q8WZ73 partner is retained. Supporting Evidence: |
| GO:0032025 response to cobalt ion | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat-donor cobalt-ion response evidence remains unresolved. Reason: The exact Q9JHX4/Ensembl ortholog transfer is preserved. A finite donor-source search did not establish and read the complete original target assay for this particular assertion. Neither a stressor label nor an expression-based evidence code would by itself make the term wrong. The existing removal lacked a demonstrated contradiction; an explicit donor-assay audit is needed before accepting or rejecting the transferred context. |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat-donor estradiol response evidence remains unresolved. Reason: The exact Q9JHX4/Ensembl ortholog transfer is preserved. A finite donor-source search did not establish and read the complete original target assay for this particular assertion. Neither a stressor label nor an expression-based evidence code would by itself make the term wrong. The existing removal lacked a demonstrated contradiction; an explicit donor-assay audit is needed before accepting or rejecting the transferred context. |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the existing LPS-response context. Reason: The rat-donor source assay has not been independently reconstructed. Human target-containing TLR4 signaling events and cytokine/substrate regulation nevertheless corroborate the broad existing response context; no direct LPS-binding activity or uniform proinflammatory effect is implied. Supporting Evidence: Reactome:R-HSA-2562541 Reactome:R-HSA-2562564 |
| GO:0032731 positive regulation of interleukin-1 beta production | IMP PMID:22267217 Dectin-1 is an extracellular pathogen sensor for the inducti... | KEEP AS NON CORE | Summary: CASP8 positively regulates IL-1beta production in the Dectin-1 context. Reason: The source distinguishes transcriptional induction from CASP8-mediated pro-IL1B processing. The official production-regulation term is broader than direct peptide maturation, so replacing the existing assertion solely by protein maturation would discard a supported regulatory component. Retain this contextual process without claiming that every IL-1beta-producing inflammasome uses CASP8. |
| GO:0032991 protein-containing complex | IDA PMID:22267217 Dectin-1 is an extracellular pathogen sensor for the inducti... | KEEP AS NON CORE | Summary: Retain broad protein-complex membership. Reason: CASP8 is incorporated into several experimentally supported assemblies, including Dectin-1-associated and death-receptor complexes. The broad term is correct but less informative than the separately represented named complexes; no single narrower complex covers every source context. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain broad protein-complex membership. Reason: CASP8 is incorporated into several experimentally supported assemblies, including Dectin-1-associated and death-receptor complexes. The broad term is correct but less informative than the separately represented named complexes; no single narrower complex covers every source context. |
| GO:0034612 response to tumor necrosis factor | IMP PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts... | KEEP AS NON CORE | Summary: CASP8 responds to TNF through regulated substrate cleavage. Reason: RIP1 processing connects CASP8 to the measured TNF response. Retain this existing contextual assertion while recognizing that CASP8/RIPK1 cleavage can alter NF-kappaB, apoptosis and necroptosis differently across cell types. |
| GO:0035877 death effector domain binding | IPI PMID:11717445 Caspase-10 is an initiator caspase in death receptor signali... | ACCEPT | Summary: CASP8 binds the FADD death-effector domain. Reason: The source explicitly addresses CASP8/CASP10 interaction with FADD through death-effector domains. Later reconstitution and interface studies corroborate domain-specific recognition. This describes the domain on the binding target, not merely the presence of DEDs within CASP8. |
| GO:0036462 TRAIL-activated apoptotic signaling pathway | IDA PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | ACCEPT | Summary: CASP8 is an effector of TRAIL-activated apoptosis. Reason: DJ-1 interferes with procaspase-8 recruitment to FADD in the target source. This supports CASP8 participation in the receptor-driven cascade without transferring DJ-1 regulatory activity to CASP8. Supporting Evidence: |
| GO:0042110 T cell activation | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | KEEP AS NON CORE | Summary: Human CASP8 deficiency supports this lymphocyte-activation context. Reason: The original review cache is abstract-only and does not expose this specific section. Independent primary human genetics explicitly documents defects in T-, B- and NK-cell activation in CASP8 deficiency, supporting these existing annotations. Clinical loss of function does not by itself specify the direct molecular step or justify an additional activation core. |
| GO:0042113 B cell activation | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | KEEP AS NON CORE | Summary: Human CASP8 deficiency supports this lymphocyte-activation context. Reason: The original review cache is abstract-only and does not expose this specific section. Independent primary human genetics explicitly documents defects in T-, B- and NK-cell activation in CASP8 deficiency, supporting these existing annotations. Clinical loss of function does not by itself specify the direct molecular step or justify an additional activation core. |
| GO:0042802 identical protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | KEEP AS NON CORE | Summary: Retain experimentally curated CASP8 self-association. Reason: The exact self-partner is preserved. Individual target-level controls in the original interaction screen or androgen-receptor paper are not fully exposed in the cached abstracts, but independent biochemical and structural studies directly establish CASP8 dimerization and DED self-assembly. Retention does not claim that both original assays were independently reverified or assign every dimer the same activity. |
| GO:0042802 identical protein binding | IPI PMID:17170703 A novel function of caspase-8 in the regulation of androgen-... | KEEP AS NON CORE | Summary: Retain experimentally curated CASP8 self-association. Reason: The exact self-partner is preserved. Individual target-level controls in the original interaction screen or androgen-receptor paper are not fully exposed in the cached abstracts, but independent biochemical and structural studies directly establish CASP8 dimerization and DED self-assembly. Retention does not claim that both original assays were independently reverified or assign every dimer the same activity. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: CASP8 regulates apoptosis through its recruitment and proteolytic functions. Reason: The original DED-family mapping or mouse ISS assertion is compatible with CASP8-mediated activation of executioner caspases and regulated assembly. The broad regulation term need not be replaced wholesale by one receptor-specific pathway. Short products and cFLIP-dependent complexes can have different effects; no universal proapoptotic action is inferred for all products. |
| GO:0043009 chordate embryonic development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain broad developmental roles as contextual annotations. Reason: The electronic developmental assertions are compatible with the reviewed record and mouse developmental evidence, but do not define additional catalytic activities. Exact tissue-specific donor experiments and the applicable survival versus differentiation mechanisms remain incompletely audited. Broadness alone is insufficient to mark a biologically plausible inherited process as over-annotation. Supporting Evidence: file:human/CASP8/CASP8-uniprot.txt |
| GO:0043065 positive regulation of apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CASP8 regulates apoptosis through its recruitment and proteolytic functions. Reason: The original DED-family mapping or mouse ISS assertion is compatible with CASP8-mediated activation of executioner caspases and regulated assembly. The broad regulation term need not be replaced wholesale by one receptor-specific pathway. Short products and cFLIP-dependent complexes can have different effects; no universal proapoptotic action is inferred for all products. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEP PMID:12761501 Large-scale identification and characterization of human gen... | KEEP AS NON CORE | Summary: Retain experimental NF-kappaB activation with a screen-access limit. Reason: IEP denotes an experimental expression-pattern annotation, not an electronic inference. The study assays human cDNAs in signaling reporters; the individual CASP8 target-table entry was not independently inspected. Separate target experiments show prodomain-dependent NF-kappaB signaling, corroborating the existing direction without claiming physiological activation by every CASP8 construct. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:12884866 Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK... | KEEP AS NON CORE | Summary: CASP8 prodomain constructs can activate NF-kappaB. Reason: The accessible source explicitly studies prodomain-only CASP8/CASP10 constructs and RIP/NIK/IKKalpha-dependent reporter activation. Preserve that construct-dependent result; it does not establish a universally catalytic or full-length CASP8 mechanism. Supporting Evidence: |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IMP PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | KEEP AS NON CORE | Summary: CASP8 can limit NF-kappaB activation during macrophage differentiation. Reason: The monocyte study links CASP8-dependent RIP1 cleavage to prevention of sustained NF-kappaB activation. This negative effect can coexist with positive signaling in different CASP8 assemblies and constructs; the two directions are not a citation contradiction. Supporting Evidence: |
| GO:0043525 positive regulation of neuron apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the existing neuronal-apoptosis context with bounded propagation confidence. Reason: CASP8 proteolysis can initiate downstream apoptotic execution, and the curated IBA/rat transfer is not contradicted by the target mechanism. The neuronal donor assay and precise PAINT node placement were not independently re-read. This retention does not assert neuron-specific CASP8 chemistry or manufacture a new neuronal process annotation. |
| GO:0043525 positive regulation of neuron apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the existing neuronal-apoptosis context with bounded propagation confidence. Reason: CASP8 proteolysis can initiate downstream apoptotic execution, and the curated IBA/rat transfer is not contradicted by the target mechanism. The neuronal donor assay and precise PAINT node placement were not independently re-read. This retention does not assert neuron-specific CASP8 chemistry or manufacture a new neuronal process annotation. |
| GO:0044297 cell body | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat-donor cell-body localization evidence remains unresolved. Reason: The Q9JHX4/Ensembl cell-body localization transfer is preserved. A finite rat-donor search did not establish and read the original compartment-specific target assay. General cytoplasmic localization does not resolve a cell-body assignment; there is also no demonstrated localization contradiction justifying removal. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CASP8 binds protein-containing signaling assemblies. Reason: Target CASP8 recruitment to FADD-containing complexes and direct DED-complex reconstitution corroborate the broad binding claim. The exact original rat donor assay remains uninspected; complex association is not automatically interpreted as direct contact with every subunit. |
| GO:0045088 regulation of innate immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CASP8 regulates innate immune responses in defined signaling complexes. Reason: Dectin-1-associated processing and TLR-associated complexes provide target-relevant corroboration for the existing mouse-derived regulation terms. Proteolysis and complex recruitment are the underlying work; no broad transfer of every mouse inflammatory phenotype or constitutive cytokine effect is asserted. |
| GO:0045088 regulation of innate immune response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CASP8 regulates innate immune responses in defined signaling complexes. Reason: Dectin-1-associated processing and TLR-associated complexes provide target-relevant corroboration for the existing mouse-derived regulation terms. Proteolysis and complex recruitment are the underlying work; no broad transfer of every mouse inflammatory phenotype or constitutive cytokine effect is asserted. |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat-donor ethanol response evidence remains unresolved. Reason: The exact Q9JHX4/Ensembl ortholog transfer is preserved. A finite donor-source search did not establish and read the complete original target assay for this particular assertion. Neither a stressor label nor an expression-based evidence code would by itself make the term wrong. The existing removal lacked a demonstrated contradiction; an explicit donor-assay audit is needed before accepting or rejecting the transferred context. |
| GO:0045651 positive regulation of macrophage differentiation | IMP PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | KEEP AS NON CORE | Summary: CASP8 proteolysis contributes to macrophage differentiation. Reason: The source explicitly places CASP8 upstream of the differentiation-associated proteolytic cascade and identifies RIP1 cleavage and altered NF-kappaB duration. Retain the existing IMP process assertion in the tested monocyte/macrophage context without extending it to every lineage. |
| GO:0045862 positive regulation of proteolysis | IDA PMID:18387192 A pathway sensor for genome-wide screens of intracellular pr... | KEEP AS NON CORE | Summary: CASP8 expression stimulates the measured proteolytic reporter pathway. Reason: The actual Results and Methods describe CASP8 transfection in 293ET cells, a dose-dependent DEVDG-cleavage reporter and a control lacking the cleavage motif. The assay can report downstream caspase activity and does not isolate direct cleavage by purified CASP8. It nevertheless supports the existing positive-regulation assertion; dismissing it merely because CASP8 is itself a protease was incorrect. Supporting Evidence: |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain broad developmental roles as contextual annotations. Reason: The electronic developmental assertions are compatible with the reviewed record and mouse developmental evidence, but do not define additional catalytic activities. Exact tissue-specific donor experiments and the applicable survival versus differentiation mechanisms remain incompletely audited. Broadness alone is insufficient to mark a biologically plausible inherited process as over-annotation. Supporting Evidence: file:human/CASP8/CASP8-uniprot.txt |
| GO:0051604 protein maturation | IDA PMID:16916640 Engineered hybrid dimers: tracking the activation pathway of... | ACCEPT | Summary: CASP8 matures procaspase-7 by limited cleavage. Reason: Author-hosted primary Results and Methods directly show recombinant CASP8-dependent cleavage/activation of human procaspase-7 and compare cleavage-site mutants. The catalytic domain constructs and optimized buffers delimit the experiment; the CASP7-focused title does not exclude a direct CASP8 assay. The evidence-anchor appendix in CASP8-notes.md records the external Figure 1C passage and primary PDF URL; the canonical cache remains abstract-only. Supporting Evidence: |
| GO:0051604 protein maturation | IDA PMID:33852854 Gasdermin E permits interleukin-1 beta release in distinct s... | ACCEPT | Summary: Retain CASP8 participation in a gasdermin-maturation cascade. Reason: The human THP-1/mouse macrophage source distinguishes apoptotic-caspase activation from GSDME cleavage at its CASP3 site. CASP8 acts upstream, and independent CASP8 cleavage of effector procaspases corroborates its participation in protein maturation. Accept the existing broad process without claiming direct CASP8 cleavage of GSDME or identical human/mouse responses. |
| GO:0051604 protein maturation | IDA PMID:35594856 Human NLRP1 is a sensor of pathogenic coronavirus 3CL protea... | ACCEPT | Summary: Retain CASP8 participation in a gasdermin-maturation cascade. Reason: Human lung-cell experiments place CASP8 activation upstream of CASP3/GSDME processing; CASP8 inhibitor evidence is distinct from CASP3/GSDME genetic tests. Independent effector-procaspase assays establish the same CASP8 maturation role. Accept the broad process while assigning the specific GSDME cut to CASP3. |
| GO:0051604 protein maturation | IEA GO_REF:0000117 | ACCEPT | Summary: CASP8 directly matures protein substrates. Reason: Direct activation of procaspase-7 and cleavage of GSDMC support the electronic maturation assertion. The product performs the cleavage rather than merely being consumed or required by the process. |
| GO:0060546 negative regulation of necroptotic process | IDA PMID:31827280 A dominant autoinflammatory disease caused by non-cleavable ... | ACCEPT | Summary: CASP8 proteolysis restrains RIPK-dependent necroptosis. Reason: Human cleavage-resistant RIPK1 variants and cellular/mouse models establish the significance of the CASP8 cleavage checkpoint. Retain the experimental and ortholog/rule assertions while preserving differences between patient blood cells, fibroblasts and mouse models. This is not a claim that CASP8 suppresses every type of necrotic death. |
| GO:0060546 negative regulation of necroptotic process | IEA GO_REF:0000120 | ACCEPT | Summary: CASP8 proteolysis restrains RIPK-dependent necroptosis. Reason: Human cleavage-resistant RIPK1 variants and cellular/mouse models establish the significance of the CASP8 cleavage checkpoint. Retain the experimental and ortholog/rule assertions while preserving differences between patient blood cells, fibroblasts and mouse models. This is not a claim that CASP8 suppresses every type of necrotic death. |
| GO:0060546 negative regulation of necroptotic process | ISS GO_REF:0000024 | ACCEPT | Summary: CASP8 proteolysis restrains RIPK-dependent necroptosis. Reason: Human cleavage-resistant RIPK1 variants and cellular/mouse models establish the significance of the CASP8 cleavage checkpoint. Retain the experimental and ortholog/rule assertions while preserving differences between patient blood cells, fibroblasts and mouse models. This is not a claim that CASP8 suppresses every type of necrotic death. |
| GO:0060715 syncytiotrophoblast cell differentiation involved in labyrinthine layer development | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | UNDECIDED | Summary: The precise placental differentiation assertion remains unresolved. Reason: The review cache does not expose the evidence for syncytiotrophoblast differentiation in labyrinthine-layer development, and the attempted full primary review access was blocked. The term and source must be checked against the actual species and developmental assay. Neither human-versus-mouse placental terminology nor a broad survival phenotype alone settles the annotation. Supporting Evidence: |
| GO:0070269 pyroptotic inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CASP8 can promote gasdermin-dependent inflammatory death. Reason: Direct GSDMC cleavage in human cancer-cell systems and CASP8-associated inflammatory pathways corroborate the existing mouse-derived pyroptotic-response context. CASP8 is the protease or upstream activator, not the pore; CASP3-mediated GSDME processing must remain distinct from direct GSDMC cleavage. |
| GO:0070269 pyroptotic inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CASP8 can promote gasdermin-dependent inflammatory death. Reason: Direct GSDMC cleavage in human cancer-cell systems and CASP8-associated inflammatory pathways corroborate the existing mouse-derived pyroptotic-response context. CASP8 is the protease or upstream activator, not the pore; CASP3-mediated GSDME processing must remain distinct from direct GSDMC cleavage. |
| GO:0071260 cellular response to mechanical stimulus | IEP PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer... | UNDECIDED | Summary: The mechanical-response citation needs a target-assay audit. Reason: The available primary source concerns BAD-dependent prostate-cancer growth; the inspected abstract and selected narrative do not establish the specific CASP8 mechanical-stimulus experiment. IEP is experimental, and a title or an unlocated passage is insufficient to declare wrong-gene attribution or remove the annotation. The exact source assay or mapping remains unresolved. Supporting Evidence: |
| GO:0071550 death-inducing signaling complex assembly | NAS PMID:38710704 Deciphering DED assembly mechanisms in FADD-procaspase-8-cFL... | ACCEPT | Summary: CASP8 contributes to DISC assembly through DED interfaces. Reason: Primary reconstitutions and interface perturbations demonstrate FADD/CASP8/cFLIP assembly. Engineered mutations suppress otherwise extensive self-filamentation to permit structural analysis, so the solved assemblies support the interaction mechanism without fixing the stoichiometry of every endogenous DISC. Supporting Evidence: |
| GO:0072347 response to anesthetic | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat-donor anesthetic response evidence remains unresolved. Reason: The exact Q9JHX4/Ensembl ortholog transfer is preserved. A finite donor-source search did not establish and read the complete original target assay for this particular assertion. Neither a stressor label nor an expression-based evidence code would by itself make the term wrong. The existing removal lacked a demonstrated contradiction; an explicit donor-assay audit is needed before accepting or rejecting the transferred context. |
| GO:0097110 scaffold protein binding | IPI PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | ACCEPT | Summary: CASP8 binds the FADD scaffold during apoptotic recruitment. Reason: The source reports DJ-1 interference with the procaspase-8/FADD interaction. The exact FADD partner is retained; this broader scaffold-binding assertion is compatible with the independently represented DED-binding mechanism and does not assign FADD scaffolding catalysis to CASP8. |
| GO:0097190 apoptotic signaling pathway | IMP PMID:11101870 Fas triggers an alternative, caspase-8-independent cell deat... | ACCEPT | Summary: Retain CASP8 participation in apoptotic signaling. Reason: The original paper also studies a caspase-independent branch, but that does not negate its CASP8 experimental annotation. The exact CASP8 control is not fully visible in the abstract; independent human DISC activation directly corroborates the same broad apoptotic-signaling function. |
| GO:0097190 apoptotic signaling pathway | TAS Reactome:R-HSA-2562564 | ACCEPT | Summary: TLR-associated CASP8 processing contributes to apoptotic signaling. Reason: These curated events describe CASP8 activation in TLR4- or TLR3-associated complexes. The apoptotic-signaling term is appropriately broader than death-domain-receptor signaling, and is retained without forcing a receptor-class replacement. |
| GO:0097190 apoptotic signaling pathway | TAS Reactome:R-HSA-9013895 | ACCEPT | Summary: TLR-associated CASP8 processing contributes to apoptotic signaling. Reason: These curated events describe CASP8 activation in TLR4- or TLR3-associated complexes. The apoptotic-signaling term is appropriately broader than death-domain-receptor signaling, and is retained without forcing a receptor-class replacement. |
| GO:0097191 extrinsic apoptotic signaling pathway | IDA PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | ACCEPT | Summary: CASP8 mediates extrinsic apoptotic signaling. Reason: The DJ-1 recruitment study and bacterial CopC inhibition study concern regulation of host CASP8-dependent death signaling. Preserve the broader existing term alongside the independently represented TRAIL descendant; CaM activation of the bacterial effector is not transferred to CASP8 as its own molecular activity. |
| GO:0097191 extrinsic apoptotic signaling pathway | IDA PMID:35446120 Calmodulin Binding Activates Chromobacterium CopC Effector t... | ACCEPT | Summary: CASP8 mediates extrinsic apoptotic signaling. Reason: The DJ-1 recruitment study and bacterial CopC inhibition study concern regulation of host CASP8-dependent death signaling. Preserve the broader existing term alongside the independently represented TRAIL descendant; CaM activation of the bacterial effector is not transferred to CASP8 as its own molecular activity. |
| GO:0097194 execution phase of apoptosis | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CASP8 can contribute to apoptotic execution as well as initiation. Reason: The official execution-phase definition permits other effectors in controlled cellular breakdown. Direct plectin cleavage by CASP8 supplies a concrete structural-substrate example; being termed an initiator does not exclude such work. The ripoptosome source primarily resolves upstream death signaling, so its specific execution phenotype is retained with curator deference and independent substrate support rather than recast as proof of a unique terminal executor. Supporting Evidence: PMID:10891503 Plectin was quantitatively cleaved by caspase 8 at Asp 2395 |
| GO:0097194 execution phase of apoptosis | IMP PMID:21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containi... | KEEP AS NON CORE | Summary: CASP8 can contribute to apoptotic execution as well as initiation. Reason: The official execution-phase definition permits other effectors in controlled cellular breakdown. Direct plectin cleavage by CASP8 supplies a concrete structural-substrate example; being termed an initiator does not exclude such work. The ripoptosome source primarily resolves upstream death signaling, so its specific execution phenotype is retained with curator deference and independent substrate support rather than recast as proof of a unique terminal executor. |
| GO:0097194 execution phase of apoptosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CASP8 can contribute to apoptotic execution as well as initiation. Reason: The official execution-phase definition permits other effectors in controlled cellular breakdown. Direct plectin cleavage by CASP8 supplies a concrete structural-substrate example; being termed an initiator does not exclude such work. The ripoptosome source primarily resolves upstream death signaling, so its specific execution phenotype is retained with curator deference and independent substrate support rather than recast as proof of a unique terminal executor. |
| GO:0097264 self proteolysis | IEA GO_REF:0000107 | ACCEPT | Summary: CASP8 undergoes activation-associated self proteolysis. Reason: The target processing study shows sequential cleavage after DISC association and release of active subunits. CASP8 participates in the cleavage chemistry; autoproteolysis is distinguished from simply being an input to another protease. Supporting Evidence: |
| GO:0097264 self proteolysis | ISS GO_REF:0000024 | ACCEPT | Summary: CASP8 undergoes activation-associated self proteolysis. Reason: The target processing study shows sequential cleavage after DISC association and release of active subunits. CASP8 participates in the cleavage chemistry; autoproteolysis is distinguished from simply being an input to another protease. Supporting Evidence: |
| GO:0097342 ripoptosome | IDA PMID:21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containi... | ACCEPT | Summary: CASP8 is a component of the ripoptosome. Reason: The source characterizes a high-molecular-weight human-cell complex containing RIP1, FADD, CASP8 and related regulators. Detection of complex association does not establish direct binding of every pair or a fixed stoichiometry under all stimuli. Supporting Evidence: |
| GO:1900119 positive regulation of execution phase of apoptosis | IDA PMID:16916640 Engineered hybrid dimers: tracking the activation pathway of... | ACCEPT | Summary: CASP8 promotes the execution phase by activating effector caspases. Reason: Recombinant CASP8 cleavage and activation of procaspase-7 provide direct mechanism for positive regulation of apoptotic execution. This is compatible with an initiator role and does not require CASP8 to perform every downstream cleavage itself. The original term should not be replaced merely because its molecular mechanism is upstream activation. The evidence-anchor appendix in CASP8-notes.md records the external Figure 1C passage and primary PDF URL; the canonical cache remains abstract-only. Supporting Evidence: |
| GO:1900119 positive regulation of execution phase of apoptosis | IEA GO_REF:0000120 | ACCEPT | Summary: CASP8 promotes the execution phase by activating effector caspases. Reason: Recombinant CASP8 cleavage and activation of procaspase-7 provide direct mechanism for positive regulation of apoptotic execution. This is compatible with an initiator role and does not require CASP8 to perform every downstream cleavage itself. The original term should not be replaced merely because its molecular mechanism is upstream activation. Supporting Evidence: |
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Download this section (compressed HTML)Q: Should CASP8 gasdermin cleavage be represented as direct gasdermin protein maturation, as regulation of pyroptotic inflammatory response, or only in GO-CAMs where the input gasdermin is explicit?
Q: Which CASP8 immune-differentiation and developmental phenotypes should remain as flat GO biological-process annotations rather than being modeled through the more direct RIPK1/necroptosis checkpoint?
Q: Should catalysis-independent CASP8 migration signaling at lamellipodia receive a specific molecular-function term distinct from cysteine endopeptidase activity and death-effector-domain binding?
Q: Which original experiment and historical curator mapping connect mouse Casp8 O89110 (MGI:1261423; IMP, J:87073 / PMID:14657025) to GO:0030690? Selected primary Results establish NDG1-triggered CASP8 activation in 293T cells but do not resolve analogous preribosomal Noc-complex membership; the term explicitly permits non-yeast analogues.
Q: Which original rat assays establish CASP8 death-receptor contact, cobalt/estradiol/ethanol/anesthetic responses and cell-body localization, and do their constructs and cellular contexts support transfer to human CASP8?
Q: What target experiment or corrected source mapping supports the CASP8 mechanical-stimulus annotation associated with the BAD prostate-cancer paper?
Q: Can the original tables and construct records resolve the remaining cross-species and isoform-qualified interaction assertions, especially mouse TRAF2/FADD/FLASH, the six neurodegeneration-network partners and the mutant-context FADD dataset?
Q: Which source experiment supports the precise syncytiotrophoblast/labyrinthine-layer differentiation assertion, including organism and the distinction between lineage differentiation and survival?
Q: How do the nine CASP8 products and cFLIP-dependent assemblies partition proteolytic activity, DED recruitment and nonapoptotic migration or immune signaling in human cells?
Experiment: Introduce separation-of-function mutations into the CASP8 tandem DEDs in a CASP8-null human epithelial or lymphoid line, then quantify DISC recruitment, effector-caspase maturation, RIPK1 cleavage, and necroptosis after FASL, TRAIL, and TNF stimulation.
Hypothesis: CASP8 DED interfaces that recruit FADD and cFLIP differentially control extrinsic apoptosis versus RIPK1 cleavage.
Type: structure-function pathway assay
Experiment: Use cells expressing noncleavable endogenous GSDMC, GSDMD, or GSDME variants together with acute CASP8 rescue or inhibition to measure direct cleavage, pore formation, and cytokine release after DR6, TAK1/NLRP1, and TNF inputs.
Hypothesis: CASP8 directly determines which gasdermin substrate is matured in epithelial pyroptotic responses.
Type: gasdermin cleavage rescue assay
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