Casp8 encodes mouse caspase-8, a tandem-death-effector-domain initiator caspase that is recruited to FADD-containing death-inducing signaling complexes and cytosolic RIPK1/FADD/cFLIP platforms. Dimerized Casp8 acts as an Asp-directed cysteine endopeptidase that initiates death-receptor apoptosis by maturing downstream caspases, restrains RIPK1/RIPK3-dependent necroptosis by cleaving death-complex substrates, and connects innate or death-receptor inputs to inflammatory cytokine and pyroptotic branches through substrates such as GSDMD and N4BP1. Mouse loss-of-function studies also reveal essential endothelial, yolk-sac, hematopoietic, and macrophage contexts for this death-complex checkpoint activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001525 angiogenesis | IMP PMID:12404118 Ex vivo whole-embryo culture of caspase-8-deficient embryos ... | KEEP AS NON CORE | Summary: This developmental phenotype is a tissue context rather than a core Casp8 molecular activity. Reason: Casp8 is essential for embryonic endothelial, yolk-sac, heart, and neural-tube development, but those organismal phenotypes are downstream of its death-complex checkpoint activities. Supporting Evidence: PMID:12404118 neural and heart defects were rescued by ex vivo whole-embryo culture |
| GO:0001525 angiogenesis | IMP PMID:31748744 Caspase-8 is the molecular switch for apoptosis, necroptosis... | KEEP AS NON CORE | Summary: This developmental phenotype is a tissue context rather than a core Casp8 molecular activity. Reason: Casp8 is essential for embryonic endothelial, yolk-sac, heart, and neural-tube development, but those organismal phenotypes are downstream of its death-complex checkpoint activities. Supporting Evidence: PMID:12404118 neural and heart defects were rescued by ex vivo whole-embryo culture |
| GO:0001817 regulation of cytokine production | IDA PMID:32971525 Integration of innate immune signalling by caspase-8 cleavag... | KEEP AS NON CORE | Summary: Casp8 cleavage of N4BP1 is a direct innate-immune and cytokine-production branch. Reason: N4BP1 cleavage by Casp8 licenses cytokine responses downstream of innate stimuli, but this inflammatory branch is secondary to the apoptosis-focused core functions. Supporting Evidence: PMID:32971525 suppressor of cytokine production that is cleaved and inactivated by caspase-8 |
| GO:0001817 regulation of cytokine production | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Casp8 cleavage of N4BP1 is a direct innate-immune and cytokine-production branch. Reason: N4BP1 cleavage by Casp8 licenses cytokine responses downstream of innate stimuli, but this inflammatory branch is secondary to the apoptosis-focused core functions. Supporting Evidence: PMID:32971525 suppressor of cytokine production that is cleaved and inactivated by caspase-8 |
| GO:0001841 neural tube formation | IMP PMID:12404118 Ex vivo whole-embryo culture of caspase-8-deficient embryos ... | KEEP AS NON CORE | Summary: This developmental phenotype is a tissue context rather than a core Casp8 molecular activity. Reason: Casp8 is essential for embryonic endothelial, yolk-sac, heart, and neural-tube development, but those organismal phenotypes are downstream of its death-complex checkpoint activities. Supporting Evidence: PMID:12404118 neural and heart defects were rescued by ex vivo whole-embryo culture |
| GO:0002682 regulation of immune system process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain broad regulation of immune-system processes. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 regulates lymphocyte homeostasis, inflammatory cytokine production and pyroptosis/necroptosis balance in immune cells; the broad ARBA term is compatible but non-core, consistent with human CASP8. |
| GO:0004175 endopeptidase activity | IDA PMID:22037414 Caspase 8 inhibits programmed necrosis by processing CYLD. | MODIFY | Summary: The generic peptidase term is correct but less specific than cysteine-type endopeptidase activity. Reason: Casp8 is an Asp-directed cysteine endopeptidase rather than merely a generic peptidase; use GO:0004197 for the catalytic activity. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004175 endopeptidase activity | IDA PMID:32971525 Integration of innate immune signalling by caspase-8 cleavag... | MODIFY | Summary: The generic peptidase term is correct but less specific than cysteine-type endopeptidase activity. Reason: Casp8 is an Asp-directed cysteine endopeptidase rather than merely a generic peptidase; use GO:0004197 for the catalytic activity. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004175 endopeptidase activity | IMP PMID:22037414 Caspase 8 inhibits programmed necrosis by processing CYLD. | MODIFY | Summary: The generic peptidase term is correct but less specific than cysteine-type endopeptidase activity. Reason: Casp8 is an Asp-directed cysteine endopeptidase rather than merely a generic peptidase; use GO:0004197 for the catalytic activity. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:12065591 Active caspase-8 translocates into the nucleus of apoptotic ... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:15456877 Vhlh gene deletion induces Hif-1-mediated cell death in thym... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16183742 Apoptosis caused by p53-induced protein with death domain (P... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: PMID:16183742 is primarily a PIDD/RAIDD paper, but its TNF positive control directly detected caspase-8 IETD cleavage activity in wild-type mouse embryonic fibroblasts. Supporting Evidence: PMID:16183742 detected activation of caspase-2 (3.3-fold), caspase-3/-7 (8.9-fold), caspase-8 (1.8-fold), and caspase-9 (2.0-fold) |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:30361383 Pathogen blockade of TAK1 triggers caspase-8-dependent cleav... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:9727491 Bid, a Bcl2 interacting protein, mediates cytochrome c relea... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: BID is a direct proximal Casp8 substrate in Fas apoptotic signaling, so this row contributes direct support for Casp8's core cysteine endopeptidase activity. Supporting Evidence: PMID:9727491 Caspase-8 cleaves Bid |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:9727492 Cleavage of BID by caspase 8 mediates the mitochondrial dama... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: BID is a specific proximal Casp8 substrate in Fas apoptotic signaling, so this row contributes direct support for Casp8's core cysteine endopeptidase activity. Supporting Evidence: PMID:9727492 a specific proximal substrate of Casp8 in the Fas apoptotic signaling pathway |
| GO:0004197 cysteine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | IGI PMID:21368763 Catalytic activity of the caspase-8-FLIP(L) complex inhibits... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:31511692 Cleavage of RIPK1 by caspase-8 is crucial for limiting apopt... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:31748744 Caspase-8 is the molecular switch for apoptosis, necroptosis... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:31827281 Mutations that prevent caspase cleavage of RIPK1 cause autoi... | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0004197 cysteine-type endopeptidase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 is an Asp-directed cysteine endopeptidase activated in death-receptor and cytosolic death complexes. Reason: Mouse Casp8 has direct biochemical support for caspase substrate cleavage, gasdermin cleavage, and RIPK1/CYLD cleavage, and the inherited caspase-family rows capture the same core catalytic activity. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0005123 death receptor binding | ISO GO_REF:0000096 | UNDECIDED | Summary: Direct death-receptor binding by Casp8 is unresolved. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Canonical recruitment places FADD between receptor death domains and Casp8 DEDs, which argues against direct receptor binding, but the rat donor assay behind this ISO transfer has not been traced; left UNDECIDED, matching human CASP8. Propagation Review Root cause: UNRESOLVED Failure modes: ROLE CONFLATION Sources checked: RGD:620945 UNRESOLVED The rat donor assay behind this ISO transfer has not been traced, so the direct receptor-binding claim cannot be confirmed or ruled out; canonical architecture places FADD between the receptor death domain and the Casp8 DEDs. |
| GO:0005164 tumor necrosis factor receptor binding | ISO GO_REF:0000096 | UNDECIDED | Summary: Direct TNF-receptor binding by Casp8 is unresolved. Reason: Ortholog audit 2026-10-12 (revised after PR #5079 review): TNFR1 is a death receptor, so this row stands or falls with the sibling GO:0005123 death receptor binding row, which was moved to UNDECIDED. Canonical recruitment places FADD between receptor death domains and Casp8 DEDs, which argues against direct receptor binding, but this is the same untraced ISO transfer from rat donor RGD:620945; per the project rule against REMOVE on untraced donor evidence it is left UNDECIDED rather than removed, matching GO:0005123. Propagation Review Root cause: UNRESOLVED Failure modes: ROLE CONFLATION Sources checked: RGD:620945 UNRESOLVED The rat donor assay behind this ISO transfer has not been traced, so the direct TNF-receptor-binding claim cannot be confirmed or ruled out; canonical architecture places FADD between the receptor death domain and the Casp8 DEDs. |
| GO:0005515 protein binding | IPI PMID:11684016 C/EBPbeta phosphorylation by RSK creates a functional XEXD c... | UNDECIDED | Summary: The cached abstract does not verify the exact Casp8 interactor behind this generic protein-binding row. Reason: GO:0005515 is uninformative, but this abstract-only record should be checked in full before deciding whether a more specific binding term is justified or the row should simply be removed. |
| GO:0005515 protein binding | IPI PMID:15383280 Inhibition of both the extrinsic and intrinsic death pathway... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005515 protein binding | IPI PMID:16469705 The E3 ubiquitin ligase itch couples JNK activation to TNFal... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005515 protein binding | IPI PMID:17159908 Palmitoylation is required for efficient Fas cell death sign... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005515 protein binding | IPI PMID:17170703 A novel function of caspase-8 in the regulation of androgen-... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005515 protein binding | IPI PMID:18455983 TIPE2, a negative regulator of innate and adaptive immunity ... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005515 protein binding | IPI PMID:18455983 TIPE2, a negative regulator of innate and adaptive immunity ... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005515 protein binding | IPI PMID:18946037 FADD and caspase-8 control the outcome of autophagic signali... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005515 protein binding | IPI PMID:21368763 Catalytic activity of the caspase-8-FLIP(L) complex inhibits... | MODIFY | Summary: The cFLIP interaction supports Casp8 assembly through death-effector/caspase-domain signaling complexes better than generic protein binding. Reason: cFLIP and Casp8 form catalytically active heterodimers that restrain RIPK3-dependent necrosis; replace the uninformative binding parent with death effector domain binding for the DED-mediated assembly role. Proposed replacements: death effector domain binding Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 |
| GO:0005515 protein binding | IPI PMID:21382479 Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced a... | UNDECIDED | Summary: The cached abstract does not verify the exact Casp8 interactor behind this generic protein-binding row. Reason: GO:0005515 is uninformative, but this abstract-only record should be checked in full before deciding whether a more specific binding term is justified or the row should simply be removed. |
| GO:0005515 protein binding | IPI PMID:24113711 Pellino3 targets RIP1 and regulates the pro-apoptotic effect... | UNDECIDED | Summary: The cached abstract does not verify the exact Casp8 interactor behind this generic protein-binding row. Reason: GO:0005515 is uninformative, but this abstract-only record should be checked in full before deciding whether a more specific binding term is justified or the row should simply be removed. |
| GO:0005515 protein binding | IPI PMID:24557836 Activity of protein kinase RIPK3 determines whether cells di... | UNDECIDED | Summary: The cached abstract does not verify the exact Casp8 interactor behind this generic protein-binding row. Reason: GO:0005515 is uninformative, but this abstract-only record should be checked in full before deciding whether a more specific binding term is justified or the row should simply be removed. |
| GO:0005515 protein binding | IPI PMID:26555174 NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma b... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005515 protein binding | IPI PMID:26649818 Phosphorylation and linear ubiquitin direct A20 inhibition o... | UNDECIDED | Summary: The cached abstract does not verify the exact Casp8 interactor behind this generic protein-binding row. Reason: GO:0005515 is uninformative, but this abstract-only record should be checked in full before deciding whether a more specific binding term is justified or the row should simply be removed. |
| GO:0005515 protein binding | IPI PMID:26649818 Phosphorylation and linear ubiquitin direct A20 inhibition o... | UNDECIDED | Summary: The cached abstract does not verify the exact Casp8 interactor behind this generic protein-binding row. Reason: GO:0005515 is uninformative, but this abstract-only record should be checked in full before deciding whether a more specific binding term is justified or the row should simply be removed. |
| GO:0005515 protein binding | IPI PMID:29440439 Death-domain dimerization-mediated activation of RIPK1 contr... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005515 protein binding | IPI PMID:31519887 K63-linked ubiquitination regulates RIPK1 kinase activity to... | REMOVE | Summary: Generic protein binding is not an informative molecular-function annotation for Casp8. Reason: The reported interaction may be real, but GO:0005515 does not describe a specific Casp8 molecular activity; DED binding, DISC assembly, ripoptosome membership, cysteine endopeptidase activity, and substrate-cleavage rows capture the informative biology. |
| GO:0005634 nucleus | IDA PMID:12065591 Active caspase-8 translocates into the nucleus of apoptotic ... | KEEP AS NON CORE | Summary: Casp8 can relocalize to the nucleus in apoptotic neurons, but this is a context-specific location. Reason: The main Casp8 locations for apoptosis and necroptosis are cytosolic death complexes; nuclear PARP-2 cleavage is a specialized apoptotic branch rather than the core site of Casp8 activation. Supporting Evidence: PMID:12065591 the nucleus of apoptotic neurons, where it cleaves PARP-2 |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Casp8 can relocalize to the nucleus in apoptotic neurons, but this is a context-specific location. Reason: The main Casp8 locations for apoptosis and necroptosis are cytosolic death complexes; nuclear PARP-2 cleavage is a specialized apoptotic branch rather than the core site of Casp8 activation. Supporting Evidence: PMID:12065591 the nucleus of apoptotic neurons, where it cleaves PARP-2 |
| GO:0005634 nucleus | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Casp8 can relocalize to the nucleus in apoptotic neurons, but this is a context-specific location. Reason: The main Casp8 locations for apoptosis and necroptosis are cytosolic death complexes; nuclear PARP-2 cleavage is a specialized apoptotic branch rather than the core site of Casp8 activation. Supporting Evidence: PMID:12065591 the nucleus of apoptotic neurons, where it cleaves PARP-2 |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm is a major location for procaspase-8 and activated Casp8 signaling complexes. Reason: Casp8 is recruited from the cytoplasm into cytosolic or receptor-proximal death-inducing complexes where proximity drives activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0005737 cytoplasm | IDA PMID:10638761 Caspase-12 mediates endoplasmic-reticulum-specific apoptosis... | UNDECIDED | Summary: This direct cytoplasm localization row is not exposed by the cached abstract. Reason: The local abstract foregrounds a neighboring caspase pathway rather than a mouse Casp8 localization assay, so the row needs full-text verification. |
| GO:0005737 cytoplasm | IDA PMID:12065591 Active caspase-8 translocates into the nucleus of apoptotic ... | ACCEPT | Summary: Cytoplasm is a major location for procaspase-8 and activated Casp8 signaling complexes. Reason: Casp8 is recruited from the cytoplasm into cytosolic or receptor-proximal death-inducing complexes where proximity drives activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasm is a major location for procaspase-8 and activated Casp8 signaling complexes. Reason: Casp8 is recruited from the cytoplasm into cytosolic or receptor-proximal death-inducing complexes where proximity drives activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0005737 cytoplasm | ISO GO_REF:0000096 | ACCEPT | Summary: Cytoplasm is a major location for procaspase-8 and activated Casp8 signaling complexes. Reason: Casp8 is recruited from the cytoplasm into cytosolic or receptor-proximal death-inducing complexes where proximity drives activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0005737 cytoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: Cytoplasm is a major location for procaspase-8 and activated Casp8 signaling complexes. Reason: Casp8 is recruited from the cytoplasm into cytosolic or receptor-proximal death-inducing complexes where proximity drives activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0005737 cytoplasm | NAS PMID:16630894 The apoptosome activates caspase-9 by dimerization. | UNDECIDED | Summary: This direct cytoplasm localization row is not exposed by the cached abstract. Reason: The local abstract foregrounds a neighboring caspase pathway rather than a mouse Casp8 localization assay, so the row needs full-text verification. |
| GO:0005739 mitochondrion | HDA PMID:18614015 A mitochondrial protein compendium elucidates complex I dise... | MARK AS OVER ANNOTATED | Summary: The MitoCarta HDA row is not strong evidence that Casp8 is a resident mitochondrial protein. Reason: Casp8 cleaves BID upstream of mitochondrial outer-membrane permeabilization, but its better-supported sites are cytosolic DISC and ripoptosome-like complexes rather than the mitochondrion itself. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Cytosol is an appropriate location for Casp8 death-complex activity. Reason: Casp8 is recruited from the cytosol into DISC and ripoptosome platforms where it dimerizes and cleaves downstream substrates. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0005829 cytosol | ISO GO_REF:0000096 | ACCEPT | Summary: Cytosol is an appropriate location for Casp8 death-complex activity. Reason: Casp8 is recruited from the cytosol into DISC and ripoptosome platforms where it dimerizes and cleaves downstream substrates. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0005829 cytosol | ISO GO_REF:0000119 | ACCEPT | Summary: Cytosol is an appropriate location for Casp8 death-complex activity. Reason: Casp8 is recruited from the cytosol into DISC and ripoptosome platforms where it dimerizes and cleaves downstream substrates. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0005829 cytosol | ISO GO_REF:0000119 | ACCEPT | Summary: Cytosol is an appropriate location for Casp8 death-complex activity. Reason: Casp8 is recruited from the cytosol into DISC and ripoptosome platforms where it dimerizes and cleaves downstream substrates. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0005886 plasma membrane | IDA PMID:10638761 Caspase-12 mediates endoplasmic-reticulum-specific apoptosis... | UNDECIDED | Summary: This plasma-membrane row is not exposed by the cached ER-stress abstract. Reason: The local abstract mentions Casp8 only as a death-receptor caspase and does not verify direct mouse Casp8 plasma-membrane localization. |
| GO:0005886 plasma membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain regulated plasma-membrane association of Casp8. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 is recruited to receptor DISCs at the cytoplasmic face of the plasma membrane and localizes to lamellipodial membrane ruffles; the broad location is compatible but non-core, matching human CASP8. DISC membership is represented separately by GO:0031264. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0006508 proteolysis | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Proteolysis is correct for Casp8 but is a broad parent of the accepted protein processing row. Reason: Ortholog audit 2026-10-12 (revised after review): Casp8 directly cleaves many protein substrates (procaspases, BID, RIPK1, CYLD, N4BP1), so the term is true and is not removed. It is strictly entailed by GO:0016485 protein processing, which is accepted as core in this file, so this broad parent is kept as non-core rather than accepted. Supporting Evidence: PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0006508 proteolysis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Proteolysis is correct for Casp8 but is a broad parent of the accepted protein processing row. Reason: Ortholog audit 2026-10-12 (revised after review): Casp8 directly cleaves many protein substrates (procaspases, BID, RIPK1, CYLD, N4BP1), so the term is true and is not removed. It is strictly entailed by GO:0016485 protein processing, which is accepted as core in this file, so this broad parent is kept as non-core rather than accepted. Supporting Evidence: PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0006915 apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Apoptotic process is correct for Casp8 but is a broad parent of the accepted extrinsic apoptotic signaling rows. Reason: Ortholog audit 2026-10-12 (revised after review): Casp8 activates executioner caspases in death-receptor DISC, TNF complex II/ripoptosome and TLR-associated platforms, so the term is true. Narrowing every broad row to GO:0008625 would wrongly exclude the non-receptor platforms, so it is not MODIFY'd; but the term is entailed by GO:0097191 and GO:0008625, which are accepted as core, so it is kept as correct but non-core. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0006915 apoptotic process | IDA PMID:16183742 Apoptosis caused by p53-induced protein with death domain (P... | MARK AS OVER ANNOTATED | Summary: The PIDD/RAIDD experiment does not support direct Casp8 involvement in the PIDD apoptotic branch. Reason: PIDD expression activated caspase-2 and effector caspases in MEFs, but the paper explicitly reports no processing of procaspase-8 in PIDD-expressing MEFs, so a generic Casp8 apoptotic-process row overstates this assay. Supporting Evidence: PMID:16183742 Processing of procaspase-8 and -9 was not detected in PIDD-expressing MEFs of either genotype |
| GO:0006915 apoptotic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Apoptotic process is correct for Casp8 but is a broad parent of the accepted extrinsic apoptotic signaling rows. Reason: Ortholog audit 2026-10-12 (revised after review): Casp8 activates executioner caspases in death-receptor DISC, TNF complex II/ripoptosome and TLR-associated platforms, so the term is true. Narrowing every broad row to GO:0008625 would wrongly exclude the non-receptor platforms, so it is not MODIFY'd; but the term is entailed by GO:0097191 and GO:0008625, which are accepted as core, so it is kept as correct but non-core. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0006915 apoptotic process | ISO GO_REF:0000008 | KEEP AS NON CORE | Summary: Apoptotic process is correct for Casp8 but is a broad parent of the accepted extrinsic apoptotic signaling rows. Reason: Ortholog audit 2026-10-12 (revised after review): Casp8 activates executioner caspases in death-receptor DISC, TNF complex II/ripoptosome and TLR-associated platforms, so the term is true. Narrowing every broad row to GO:0008625 would wrongly exclude the non-receptor platforms, so it is not MODIFY'd; but the term is entailed by GO:0097191 and GO:0008625, which are accepted as core, so it is kept as correct but non-core. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0006915 apoptotic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Apoptotic process is correct for Casp8 but is a broad parent of the accepted extrinsic apoptotic signaling rows. Reason: Ortholog audit 2026-10-12 (revised after review): Casp8 activates executioner caspases in death-receptor DISC, TNF complex II/ripoptosome and TLR-associated platforms, so the term is true. Narrowing every broad row to GO:0008625 would wrongly exclude the non-receptor platforms, so it is not MODIFY'd; but the term is entailed by GO:0097191 and GO:0008625, which are accepted as core, so it is kept as correct but non-core. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0007507 heart development | IMP PMID:12404118 Ex vivo whole-embryo culture of caspase-8-deficient embryos ... | KEEP AS NON CORE | Summary: This developmental phenotype is a tissue context rather than a core Casp8 molecular activity. Reason: Casp8 is essential for embryonic endothelial, yolk-sac, heart, and neural-tube development, but those organismal phenotypes are downstream of its death-complex checkpoint activities. Supporting Evidence: PMID:12404118 neural and heart defects were rescued by ex vivo whole-embryo culture |
| GO:0007507 heart development | IMP PMID:31748744 Caspase-8 is the molecular switch for apoptosis, necroptosis... | KEEP AS NON CORE | Summary: This developmental phenotype is a tissue context rather than a core Casp8 molecular activity. Reason: Casp8 is essential for embryonic endothelial, yolk-sac, heart, and neural-tube development, but those organismal phenotypes are downstream of its death-complex checkpoint activities. Supporting Evidence: PMID:12404118 neural and heart defects were rescued by ex vivo whole-embryo culture |
| GO:0008233 peptidase activity | IDA PMID:11369777 Activation of pro-death Bcl-2 family proteins and mitochondr... | UNDECIDED | Summary: The cached TNF/Bid liver-injury abstract does not expose a direct Casp8 peptidase assay. Reason: The row may reflect real Casp8 activation downstream of TNF, but the local abstract does not show whether mouse Casp8 enzymatic activity itself was assayed; leave this direct molecular-function assertion undecided pending full text. |
| GO:0008233 peptidase activity | IEA GO_REF:0000107 | MODIFY | Summary: Peptidase activity is correct but less specific than cysteine-type endopeptidase activity. Reason: Use GO:0004197 because Casp8 cleaves internal peptide bonds after Asp residues. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q14790 SUPPORTS SOURCE BUT NOT TARGET Use GO:0004197 because Casp8 cleaves internal peptide bonds after Asp residues. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0008233 peptidase activity | IMP PMID:12404118 Ex vivo whole-embryo culture of caspase-8-deficient embryos ... | MODIFY | Summary: Peptidase activity is correct but less specific than cysteine-type endopeptidase activity. Reason: The Casp8-deficient embryo phenotype depends on Casp8's protease activity; use GO:0004197 because Casp8 specifically cleaves internal peptide bonds after Asp residues. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:12404118 neural and heart defects were rescued by ex vivo whole-embryo culture |
| GO:0008233 peptidase activity | ISO GO_REF:0000119 | MODIFY | Summary: Peptidase activity is correct but less specific than cysteine-type endopeptidase activity. Reason: Use GO:0004197 because Casp8 cleaves internal peptide bonds after Asp residues. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q14790 SUPPORTS SOURCE BUT NOT TARGET Use GO:0004197 because Casp8 cleaves internal peptide bonds after Asp residues. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000002 | MODIFY | Summary: The generic peptidase term is correct but less specific than cysteine-type endopeptidase activity. Reason: Casp8 is an Asp-directed cysteine endopeptidase rather than merely a generic peptidase; use GO:0004197 for the catalytic activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR015917 SUPPORTS SOURCE BUT NOT TARGET Casp8 is an Asp-directed cysteine endopeptidase rather than merely a generic peptidase; use GO:0004197 for the catalytic activity. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0008303 caspase complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Casp8 forms catalytic caspase complexes, but the specific DISC and ripoptosome terms are more informative. Reason: Casp8 dimerizes and can assemble with cFLIP in mature catalytic complexes; keep the broad complex row as secondary context for more specific DISC and ripoptosome membership. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 |
| GO:0008303 caspase complex | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Casp8 forms catalytic caspase complexes, but the specific DISC and ripoptosome terms are more informative. Reason: Casp8 dimerizes and can assemble with cFLIP in mature catalytic complexes; keep the broad complex row as secondary context for more specific DISC and ripoptosome membership. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IBA GO_REF:0000033 | ACCEPT | Summary: Casp8 is a central initiator caspase in death-domain receptor extrinsic apoptotic signaling. Reason: FADD recruits procaspase-8 to activated death receptors, enabling DISC-dependent Casp8 activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IEA GO_REF:0000120 | ACCEPT | Summary: Casp8 is a central initiator caspase in death-domain receptor extrinsic apoptotic signaling. Reason: FADD recruits procaspase-8 to activated death receptors, enabling DISC-dependent Casp8 activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IMP PMID:15322156 Caspase-8 serves both apoptotic and nonapoptotic roles. | ACCEPT | Summary: Casp8 is a central initiator caspase in death-domain receptor extrinsic apoptotic signaling. Reason: FADD recruits procaspase-8 to activated death receptors, enabling DISC-dependent Casp8 activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 is a central initiator caspase in death-domain receptor extrinsic apoptotic signaling. Reason: FADD recruits procaspase-8 to activated death receptors, enabling DISC-dependent Casp8 activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | NAS PMID:21368762 RIP3 mediates the embryonic lethality of caspase-8-deficient... | ACCEPT | Summary: Casp8 is a central initiator caspase in death-domain receptor extrinsic apoptotic signaling. Reason: FADD recruits procaspase-8 to activated death receptors, enabling DISC-dependent Casp8 activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | TAS PMID:29053143 MOMP, cell suicide as a BCL-2 family business. | ACCEPT | Summary: Casp8 is a central initiator caspase in death-domain receptor extrinsic apoptotic signaling. Reason: FADD recruits procaspase-8 to activated death receptors, enabling DISC-dependent Casp8 activation. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process | IDA PMID:9837723 Molecular cloning and identification of murine caspase-8. | MODIFY | Summary: Casp8 activates downstream apoptotic caspases by proteolytic maturation. 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: GO:0008656 is the apoptosis-scoped cysteine-type endopeptidase activator activity; recombinant mouse Casp8 processing of murine procaspases is direct evidence that Casp8 proteolytically activates downstream caspases. 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: PMID:9837723 are processed by recombinant murine caspase-8 |
| 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: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 promotes NF-kappaB and inflammatory cytokine signaling in some complexes (separately annotated); this broad ARBA row is compatible but non-core, consistent with human CASP8. |
| GO:0016485 protein processing | IDA PMID:30361383 Pathogen blockade of TAK1 triggers caspase-8-dependent cleav... | ACCEPT | Summary: Casp8 performs limited proteolytic protein processing. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Autoprocessing and cleavage of procaspase and gasdermin precursors are catalysed by Casp8 itself, directly supporting protein processing; treated as in human CASP8. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0016485 protein processing | ISO GO_REF:0000096 | ACCEPT | Summary: Casp8 performs limited proteolytic protein processing. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Autoprocessing and cleavage of procaspase and gasdermin precursors are catalysed by Casp8 itself, directly supporting protein processing; treated as in human CASP8. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0030027 lamellipodium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lamellipodium and cell-migration rows are contextual signaling branches rather than apoptosis-core annotations. Reason: Casp8 has a reported catalysis-independent migration branch in mammals, but this context is secondary to DISC recruitment, substrate cleavage, and necroptosis restraint. |
| GO:0030027 lamellipodium | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Lamellipodium and cell-migration rows are contextual signaling branches rather than apoptosis-core annotations. Reason: Casp8 has a reported catalysis-independent migration branch in mammals, but this context is secondary to DISC recruitment, substrate cleavage, and necroptosis restraint. |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Casp8 contributes to differentiation in defined cell contexts. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 proteolysis is required for macrophage differentiation (separately annotated by IMP/IBA), supporting this broad ARBA row as contextual and non-core, consistent with human CASP8. |
| GO:0030163 protein catabolic process | IDA PMID:32971525 Integration of innate immune signalling by caspase-8 cleavag... | KEEP AS NON CORE | Summary: Casp8 cleavage of RIPK1 and other substrates is direct protein proteolysis but this process term is broad. Reason: Protein catabolic process is a broad parent for individual Casp8 substrate-cleavage events and is less informative than RIPK1 cleavage, effector-caspase maturation, and gasdermin cleavage. Supporting Evidence: PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0030163 protein catabolic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Casp8 cleavage of RIPK1 and other substrates is direct protein proteolysis but this process term is broad. Reason: Protein catabolic process is a broad parent for individual Casp8 substrate-cleavage events and is less informative than RIPK1 cleavage, effector-caspase maturation, and gasdermin cleavage. Supporting Evidence: PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0030163 protein catabolic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Casp8 cleavage of RIPK1 and other substrates is direct protein proteolysis but this process term is broad. Reason: Protein catabolic process is a broad parent for individual Casp8 substrate-cleavage events and is less informative than RIPK1 cleavage, effector-caspase maturation, and gasdermin cleavage. Supporting Evidence: PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0030225 macrophage differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Macrophage differentiation is a non-core cellular context for Casp8 signaling. Reason: Casp8 participates in myelomonocytic survival and differentiation, but this developmental outcome is secondary to its death-complex signaling and substrate-cleavage activities. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0030225 macrophage differentiation | IMP PMID:15322156 Caspase-8 serves both apoptotic and nonapoptotic roles. | KEEP AS NON CORE | Summary: Macrophage differentiation is a non-core cellular context for Casp8 signaling. Reason: Casp8 participates in myelomonocytic survival and differentiation, but this developmental outcome is secondary to its death-complex signaling and substrate-cleavage activities. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0030225 macrophage differentiation | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | KEEP AS NON CORE | Summary: Macrophage differentiation is a non-core cellular context for Casp8 signaling. Reason: Casp8 participates in myelomonocytic survival and differentiation, but this developmental outcome is secondary to its death-complex signaling and substrate-cleavage activities. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0030335 positive regulation of cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lamellipodium and cell-migration rows are contextual signaling branches rather than apoptosis-core annotations. Reason: Casp8 has a reported catalysis-independent migration branch in mammals, but this context is secondary to DISC recruitment, substrate cleavage, and necroptosis restraint. |
| GO:0030335 positive regulation of cell migration | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Lamellipodium and cell-migration rows are contextual signaling branches rather than apoptosis-core annotations. Reason: Casp8 has a reported catalysis-independent migration branch in mammals, but this context is secondary to DISC recruitment, substrate cleavage, and necroptosis restraint. |
| GO:0030690 Noc1p-Noc2p complex | IMP PMID:14657025 Transcriptional activation of known and novel apoptotic path... | UNDECIDED | Summary: Casp8 membership in a Noc1p-Noc2p (preribosomal) complex is unverified. Reason: Ortholog audit 2026-10-12 (revised after review): aligned with human CASP8. The GO term is not yeast-only, as its official comment permits the term to be used for analogous complexes in other eukaryotes, so term scope does not exclude a mammalian assignment. The cached abstract does not describe preribosomal complex membership, but this is an MGI experimental (IMP) row whose full text and curation mapping have not been inspected here, so membership is genuinely unresolved and the row is left UNDECIDED rather than removed. The human CASP8 review reached the same UNDECIDED verdict for the electronic transfer of this row. Supporting Evidence: GO:0030690 the term nevertheless can be used for analogous complexes in other eukaryotes |
| GO:0031264 death-inducing signaling complex | IEA GO_REF:0000107 | ACCEPT | Summary: Casp8 is recruited into death-inducing signaling complexes through death-effector-domain interactions. Reason: Casp8 recruitment to receptor-proximal FADD complexes is the initiating assembly step for death-receptor apoptotic signaling. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0031264 death-inducing signaling complex | ISO GO_REF:0000096 | ACCEPT | Summary: Casp8 is recruited into death-inducing signaling complexes through death-effector-domain interactions. Reason: Casp8 recruitment to receptor-proximal FADD complexes is the initiating assembly step for death-receptor apoptotic signaling. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0031264 death-inducing signaling complex | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 is recruited into death-inducing signaling complexes through death-effector-domain interactions. Reason: Casp8 recruitment to receptor-proximal FADD complexes is the initiating assembly step for death-receptor apoptotic signaling. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0031265 CD95 death-inducing signaling complex | IBA GO_REF:0000033 | ACCEPT | Summary: Casp8 is recruited into death-inducing signaling complexes through death-effector-domain interactions. Reason: Casp8 recruitment to receptor-proximal FADD complexes is the initiating assembly step for death-receptor apoptotic signaling. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0031265 CD95 death-inducing signaling complex | IEA GO_REF:0000107 | ACCEPT | Summary: Casp8 is recruited into death-inducing signaling complexes through death-effector-domain interactions. Reason: Casp8 recruitment to receptor-proximal FADD complexes is the initiating assembly step for death-receptor apoptotic signaling. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0031265 CD95 death-inducing signaling complex | ISO GO_REF:0000096 | ACCEPT | Summary: Casp8 is recruited into death-inducing signaling complexes through death-effector-domain interactions. Reason: Casp8 recruitment to receptor-proximal FADD complexes is the initiating assembly step for death-receptor apoptotic signaling. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0031265 CD95 death-inducing signaling complex | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 is recruited into death-inducing signaling complexes through death-effector-domain interactions. Reason: Casp8 recruitment to receptor-proximal FADD complexes is the initiating assembly step for death-receptor apoptotic signaling. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding is a secondary Casp8 regulatory interaction. Reason: Casp8 is regulated by ubiquitin ligases in death-ligand pathways, but those interactions are contextual relative to its direct DED recruitment and substrate cleavage. |
| GO:0031625 ubiquitin protein ligase binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding is a secondary Casp8 regulatory interaction. Reason: Casp8 is regulated by ubiquitin ligases in death-ligand pathways, but those interactions are contextual relative to its direct DED recruitment and substrate cleavage. |
| GO:0032731 positive regulation of interleukin-1 beta production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Casp8 cleavage of N4BP1 is a direct innate-immune and cytokine-production branch. Reason: N4BP1 cleavage by Casp8 licenses cytokine responses downstream of innate stimuli, but this inflammatory branch is secondary to the apoptosis-focused core functions. Supporting Evidence: PMID:32971525 suppressor of cytokine production that is cleaved and inactivated by caspase-8 |
| GO:0032731 positive regulation of interleukin-1 beta production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Casp8 cleavage of N4BP1 is a direct innate-immune and cytokine-production branch. Reason: N4BP1 cleavage by Casp8 licenses cytokine responses downstream of innate stimuli, but this inflammatory branch is secondary to the apoptosis-focused core functions. Supporting Evidence: PMID:32971525 suppressor of cytokine production that is cleaved and inactivated by caspase-8 |
| GO:0032991 protein-containing complex | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The protein-containing complex row is a generic projection of Casp8 death-complex membership. Reason: Casp8 acts in several protein complexes, but generic protein-containing complex membership is less useful than DISC and ripoptosome terms. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0032991 protein-containing complex | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: The protein-containing complex row is a generic projection of Casp8 death-complex membership. Reason: Casp8 acts in several protein complexes, but generic protein-containing complex membership is less useful than DISC and ripoptosome terms. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0032991 protein-containing complex | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: The protein-containing complex row is a generic projection of Casp8 death-complex membership. Reason: Casp8 acts in several protein complexes, but generic protein-containing complex membership is less useful than DISC and ripoptosome terms. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0034612 response to tumor necrosis factor | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TNF response is an upstream receptor context for Casp8 death-complex signaling. Reason: TNF can feed into Casp8-containing complex II and ripoptosome biology, but Casp8 itself executes cleavage and scaffold functions after receptor stimulation. Supporting Evidence: PMID:22089168 FADD, caspase-8 and c-FLIP, counteract TNF-induced necroptosis |
| GO:0034612 response to tumor necrosis factor | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: TNF response is an upstream receptor context for Casp8 death-complex signaling. Reason: TNF can feed into Casp8-containing complex II and ripoptosome biology, but Casp8 itself executes cleavage and scaffold functions after receptor stimulation. Supporting Evidence: PMID:22089168 FADD, caspase-8 and c-FLIP, counteract TNF-induced necroptosis |
| GO:0035877 death effector domain binding | IEA GO_REF:0000107 | ACCEPT | Summary: Death-effector-domain binding is the specific adaptor interaction that recruits Casp8 into FADD-containing complexes. Reason: Casp8 tandem DEDs mediate FADD/cFLIP signaling-complex assembly upstream of activation. Supporting Evidence: PMID:22675671 caspase-8-FLIP heterodimers prevent RIPK3 activation |
| GO:0035877 death effector domain binding | ISO GO_REF:0000119 | ACCEPT | Summary: Death-effector-domain binding is the specific adaptor interaction that recruits Casp8 into FADD-containing complexes. Reason: Casp8 tandem DEDs mediate FADD/cFLIP signaling-complex assembly upstream of activation. Supporting Evidence: PMID:22675671 caspase-8-FLIP heterodimers prevent RIPK3 activation |
| GO:0036462 TRAIL-activated apoptotic signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Casp8 is the initiator caspase of TRAIL-activated apoptosis. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. TRAIL receptor DISCs recruit Casp8 via FADD and Casp8 catalysis drives the cascade; the human source experiment (DJ-1 interference with procaspase-8 recruitment to FADD) is accepted for human CASP8, and the ortholog transfer is accepted here for consistency. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0036462 TRAIL-activated apoptotic signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 is the initiator caspase of TRAIL-activated apoptosis. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. TRAIL receptor DISCs recruit Casp8 via FADD and Casp8 catalysis drives the cascade; the human source experiment (DJ-1 interference with procaspase-8 recruitment to FADD) is accepted for human CASP8, and the ortholog transfer is accepted here for consistency. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Casp8 self-associates (dimerizes) during activation. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. DED-mediated assembly promotes Casp8 dimerization in DISC and ripoptosome platforms, so self-binding is real; but as a binding term it describes the activation mechanism rather than the core catalytic activity, and is kept non-core as for human CASP8. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 |
| GO:0042802 identical protein binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Casp8 self-associates (dimerizes) during activation. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. DED-mediated assembly promotes Casp8 dimerization in DISC and ripoptosome platforms, so self-binding is real; but as a binding term it describes the activation mechanism rather than the core catalytic activity, and is kept non-core as for human CASP8. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Casp8 regulates apoptosis through recruitment and proteolysis. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The broad regulation term is compatible with Casp8 activation of executioner caspases and with cFLIP-modulated outputs; it need not be replaced wholesale by one receptor-specific pathway. Kept non-core, matching human CASP8. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0043009 chordate embryonic development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain broad developmental roles as contextual annotations. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8-null mice die at midgestation through unrestrained RIPK3/MLKL necroptosis, which Casp8 normally restrains by cleaving RIPK1. Embryonic development is a compatible contextual process, not a core function; kept non-core as in human CASP8. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:9654089 Molecular cloning and characterization of mouse caspase-8. | KEEP AS NON CORE | Summary: Casp8 positively regulates apoptosis. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 promotes apoptosis by maturing downstream caspases; the mouse experimental rows are retained as non-core regulation rather than recast to GO:0008625 (which is not a descendant of this term), matching human CASP8. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:24813849 RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and ... | KEEP AS NON CORE | Summary: Casp8 positively regulates apoptosis. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 promotes apoptosis by maturing downstream caspases; the mouse experimental rows are retained as non-core regulation rather than recast to GO:0008625 (which is not a descendant of this term), matching human CASP8. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:24813850 RIPK1 blocks early postnatal lethality mediated by caspase-8... | KEEP AS NON CORE | Summary: Casp8 positively regulates apoptosis. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 promotes apoptosis by maturing downstream caspases; the mouse experimental rows are retained as non-core regulation rather than recast to GO:0008625 (which is not a descendant of this term), matching human CASP8. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:9654089 Molecular cloning and characterization of mouse caspase-8. | KEEP AS NON CORE | Summary: Casp8 positively regulates apoptosis. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 promotes apoptosis by maturing downstream caspases; the mouse experimental rows are retained as non-core regulation rather than recast to GO:0008625 (which is not a descendant of this term), matching human CASP8. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: NF-kappaB signaling is a non-core survival/inflammatory branch of Casp8 death-complex biology. Reason: Casp8-containing complexes can influence canonical NF-kappaB signaling, but this is secondary to the direct apoptosis, necroptosis-checkpoint, and substrate-cleavage roles. Supporting Evidence: PMID:32971525 suppressor of cytokine production that is cleaved and inactivated by caspase-8 |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: NF-kappaB signaling is a non-core survival/inflammatory branch of Casp8 death-complex biology. Reason: Casp8-containing complexes can influence canonical NF-kappaB signaling, but this is secondary to the direct apoptosis, necroptosis-checkpoint, and substrate-cleavage roles. Supporting Evidence: PMID:32971525 suppressor of cytokine production that is cleaved and inactivated by caspase-8 |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: NF-kappaB signaling is a non-core survival/inflammatory branch of Casp8 death-complex biology. Reason: Casp8-containing complexes can influence canonical NF-kappaB signaling, but this is secondary to the direct apoptosis, necroptosis-checkpoint, and substrate-cleavage roles. Supporting Evidence: PMID:32971525 suppressor of cytokine production that is cleaved and inactivated by caspase-8 |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: NF-kappaB signaling is a non-core survival/inflammatory branch of Casp8 death-complex biology. Reason: Casp8-containing complexes can influence canonical NF-kappaB signaling, but this is secondary to the direct apoptosis, necroptosis-checkpoint, and substrate-cleavage roles. Supporting Evidence: PMID:32971525 suppressor of cytokine production that is cleaved and inactivated by caspase-8 |
| GO:0043525 positive regulation of neuron apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: This cell-type-specific apoptosis row is a contextual branch of Casp8 death signaling. Reason: The evidence supports Casp8-dependent apoptosis in a particular tissue or stimulus context, but the direct work is better captured by death-receptor signaling and substrate cleavage. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0043525 positive regulation of neuron apoptotic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: This cell-type-specific apoptosis row is a contextual branch of Casp8 death signaling. Reason: The evidence supports Casp8-dependent apoptosis in a particular tissue or stimulus context, but the direct work is better captured by death-receptor signaling and substrate cleavage. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0044297 cell body | ISO GO_REF:0000096 | UNDECIDED | Summary: Rat-donor cell-body localization of Casp8 is unresolved. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The ISO transfer from rat has not been traced to its original compartment-specific assay. General cytoplasmic localization does not establish a cell-body assignment, but there is also no contradiction justifying removal; left UNDECIDED, matching human CASP8. Propagation Review Root cause: UNRESOLVED Failure modes: GRANULARITY MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: RGD:620945 UNRESOLVED The rat donor assay behind this ISO transfer has not been traced to its original compartment-specific context; general cytoplasmic localization does not establish a cell-body assignment, but there is no contradiction justifying removal. |
| GO:0044877 protein-containing complex binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Casp8 binds protein-containing signaling assemblies. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 is recruited into FADD-containing DISC, TNF complex II and ripoptosome assemblies, corroborating this broad binding claim; kept non-core, matching human CASP8. |
| GO:0045088 regulation of innate immune response | IDA PMID:32971525 Integration of innate immune signalling by caspase-8 cleavag... | KEEP AS NON CORE | Summary: Casp8 cleavage of N4BP1 is a direct innate-immune and cytokine-production branch. Reason: N4BP1 cleavage by Casp8 licenses cytokine responses downstream of innate stimuli, but this inflammatory branch is secondary to the apoptosis-focused core functions. Supporting Evidence: PMID:32971525 suppressor of cytokine production that is cleaved and inactivated by caspase-8 |
| GO:0045471 response to ethanol | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: This propagated high-level or generic row is not an informative direct Casp8 annotation. Reason: Local mouse and human evidence supports cytosolic death-complex recruitment, cysteine endopeptidase activity, RIPK1/GSDMD/N4BP1 cleavage, and necroptosis restraint rather than this broad propagated context. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: RGD:620945 SUPPORTS SOURCE BUT NOT TARGET Local mouse and human evidence supports cytosolic death-complex recruitment, cysteine endopeptidase activity, RIPK1/GSDMD/N4BP1 cleavage, and necroptosis restraint rather than this broad propagated context. |
| GO:0045651 positive regulation of macrophage differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Macrophage differentiation is a non-core cellular context for Casp8 signaling. Reason: Casp8 participates in myelomonocytic survival and differentiation, but this developmental outcome is secondary to its death-complex signaling and substrate-cleavage activities. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0045651 positive regulation of macrophage differentiation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Macrophage differentiation is a non-core cellular context for Casp8 signaling. Reason: Casp8 participates in myelomonocytic survival and differentiation, but this developmental outcome is secondary to its death-complex signaling and substrate-cleavage activities. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0045862 positive regulation of proteolysis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Casp8 promotes downstream proteolytic cascades. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 activation stimulates downstream caspase proteolysis; the row is compatible and kept non-core rather than replaced, matching human CASP8. Direct substrate maturation is captured by GO:0051604. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0045862 positive regulation of proteolysis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Casp8 promotes downstream proteolytic cascades. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8 activation stimulates downstream caspase proteolysis; the row is compatible and kept non-core rather than replaced, matching human CASP8. Direct substrate maturation is captured by GO:0051604. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain broad developmental roles as contextual annotations. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Casp8-null mice die at midgestation with yolk-sac vascular and heart defects through unrestrained RIPK3/MLKL necroptosis, and Casp8 cleavage of RIPK1 does the protective work. The broad ARBA developmental term is therefore biologically compatible but not a core function; kept non-core as in human CASP8. |
| GO:0048738 cardiac muscle tissue development | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | KEEP AS NON CORE | Summary: This developmental phenotype is a tissue context rather than a core Casp8 molecular activity. Reason: Casp8 is essential for embryonic endothelial, yolk-sac, heart, and neural-tube development, but those organismal phenotypes are downstream of its death-complex checkpoint activities. Supporting Evidence: PMID:12404118 neural and heart defects were rescued by ex vivo whole-embryo culture |
| GO:0051604 protein maturation | IEA GO_REF:0000120 | ACCEPT | Summary: Casp8 proteolytically matures procaspases and gasdermin-family substrates. Reason: Protein maturation captures Casp8 cleavage of inactive precursors such as procaspases and GSDMD to generate active products. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 PMID:30361383 increased concentrations of mouse and human caspase-8 cleaved GSDMD |
| GO:0051604 protein maturation | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 proteolytically matures procaspases and gasdermin-family substrates. Reason: Protein maturation captures Casp8 cleavage of inactive precursors such as procaspases and GSDMD to generate active products. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 PMID:30361383 increased concentrations of mouse and human caspase-8 cleaved GSDMD |
| GO:0051604 protein maturation | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 proteolytically matures procaspases and gasdermin-family substrates. Reason: Protein maturation captures Casp8 cleavage of inactive precursors such as procaspases and GSDMD to generate active products. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 PMID:30361383 increased concentrations of mouse and human caspase-8 cleaved GSDMD |
| GO:0060546 negative regulation of necroptotic process | IEA GO_REF:0000120 | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IGI PMID:21368763 Catalytic activity of the caspase-8-FLIP(L) complex inhibits... | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IGI PMID:21368763 Catalytic activity of the caspase-8-FLIP(L) complex inhibits... | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IGI PMID:21368763 Catalytic activity of the caspase-8-FLIP(L) complex inhibits... | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IGI PMID:21402742 Mechanisms of necroptosis in T cells. | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IGI PMID:22037414 Caspase 8 inhibits programmed necrosis by processing CYLD. | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IGI PMID:22037414 Caspase 8 inhibits programmed necrosis by processing CYLD. | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IGI PMID:22089168 TNF-induced necroptosis in L929 cells is tightly regulated b... | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IMP PMID:31511692 Cleavage of RIPK1 by caspase-8 is crucial for limiting apopt... | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IMP PMID:31748744 Caspase-8 is the molecular switch for apoptosis, necroptosis... | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | IMP PMID:31827281 Mutations that prevent caspase cleavage of RIPK1 cause autoi... | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0060546 negative regulation of necroptotic process | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 negatively regulates necroptosis by cleaving RIPK1, CYLD, and related death-complex substrates. Reason: Catalytically active FADD-Casp8-cFLIP complexes restrain RIPK1/RIPK3-dependent necroptosis and thereby prevent inflammatory embryonic and adult tissue damage. Supporting Evidence: PMID:21368763 FLIP can impart catalytic activity to non-cleavable caspase-8 PMID:22037414 Therefore, CASPASE 8 directly cleaves CYLD |
| GO:0070243 regulation of thymocyte apoptotic process | IGI PMID:15456877 Vhlh gene deletion induces Hif-1-mediated cell death in thym... | KEEP AS NON CORE | Summary: This cell-type-specific apoptosis row is a contextual branch of Casp8 death signaling. Reason: The evidence supports Casp8-dependent apoptosis in a particular tissue or stimulus context, but the direct work is better captured by death-receptor signaling and substrate cleavage. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0070269 pyroptotic inflammatory response | IDA PMID:30361383 Pathogen blockade of TAK1 triggers caspase-8-dependent cleav... | KEEP AS NON CORE | Summary: Casp8 can route TAK1-blockade inputs to GSDMD cleavage and pyroptotic inflammatory cell death. Reason: The gasdermin-D branch is direct, but it is an inflammatory cell-death output rather than the core death-receptor apoptosis or RIPK1-necroptosis checkpoint. Supporting Evidence: PMID:30361383 increased concentrations of mouse and human caspase-8 cleaved GSDMD |
| GO:0070269 pyroptotic inflammatory response | IMP PMID:31748744 Caspase-8 is the molecular switch for apoptosis, necroptosis... | KEEP AS NON CORE | Summary: Casp8 can route TAK1-blockade inputs to GSDMD cleavage and pyroptotic inflammatory cell death. Reason: The gasdermin-D branch is direct, but it is an inflammatory cell-death output rather than the core death-receptor apoptosis or RIPK1-necroptosis checkpoint. Supporting Evidence: PMID:30361383 increased concentrations of mouse and human caspase-8 cleaved GSDMD |
| GO:0070269 pyroptotic inflammatory response | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Casp8 can route TAK1-blockade inputs to GSDMD cleavage and pyroptotic inflammatory cell death. Reason: The gasdermin-D branch is direct, but it is an inflammatory cell-death output rather than the core death-receptor apoptosis or RIPK1-necroptosis checkpoint. Supporting Evidence: PMID:30361383 increased concentrations of mouse and human caspase-8 cleaved GSDMD |
| GO:0071260 cellular response to mechanical stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This propagated high-level or generic row is not an informative direct Casp8 annotation. Reason: Local mouse and human evidence supports cytosolic death-complex recruitment, cysteine endopeptidase activity, RIPK1/GSDMD/N4BP1 cleavage, and necroptosis restraint rather than this broad propagated context. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:Q14790 SUPPORTS SOURCE BUT NOT TARGET Local mouse and human evidence supports cytosolic death-complex recruitment, cysteine endopeptidase activity, RIPK1/GSDMD/N4BP1 cleavage, and necroptosis restraint rather than this broad propagated context. |
| GO:0097110 scaffold protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Casp8 binds the FADD scaffold during apoptotic recruitment. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The ortholog source (human IPI, procaspase-8/FADD interaction) is accepted for human CASP8. FADD is the scaffold through which Casp8 is recruited; the more specific DED-binding mechanism is represented separately by GO:0035877 rather than by replacing this row. Supporting Evidence: PMID:22675671 caspase-8-FLIP heterodimers prevent RIPK3 activation |
| GO:0097110 scaffold protein binding | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 binds the FADD scaffold during apoptotic recruitment. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The ortholog source (human IPI, procaspase-8/FADD interaction) is accepted for human CASP8. FADD is the scaffold through which Casp8 is recruited; the more specific DED-binding mechanism is represented separately by GO:0035877 rather than by replacing this row. Supporting Evidence: PMID:22675671 caspase-8-FLIP heterodimers prevent RIPK3 activation |
| GO:0097190 apoptotic signaling pathway | IDA PMID:16183742 Apoptosis caused by p53-induced protein with death domain (P... | MARK AS OVER ANNOTATED | Summary: The PIDD/RAIDD experiment does not support direct Casp8 involvement in PIDD apoptotic signaling. Reason: The study detected caspase-2 and effector-caspase activation after PIDD expression, but it explicitly failed to detect procaspase-8 processing in PIDD-expressing MEFs. Supporting Evidence: PMID:16183742 Processing of procaspase-8 and -9 was not detected in PIDD-expressing MEFs of either genotype |
| GO:0097190 apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Apoptotic signaling pathway is correct for Casp8 but is a broad parent of the accepted extrinsic apoptotic signaling rows. Reason: Ortholog audit 2026-10-12 (revised after review): Casp8 is the apical protease of several apoptotic signaling routes (death-domain receptors, TNF complex II, ripoptosome/TLR contexts), so the term is true and should not be forced to a single receptor-class replacement. It is entailed by GO:0097191 extrinsic apoptotic signaling pathway, accepted as core here, so it is kept as non-core. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097190 apoptotic signaling pathway | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Apoptotic signaling pathway is correct for Casp8 but is a broad parent of the accepted extrinsic apoptotic signaling rows. Reason: Ortholog audit 2026-10-12 (revised after review): Casp8 is the apical protease of several apoptotic signaling routes (death-domain receptors, TNF complex II, ripoptosome/TLR contexts), so the term is true and should not be forced to a single receptor-class replacement. It is entailed by GO:0097191 extrinsic apoptotic signaling pathway, accepted as core here, so it is kept as non-core. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097191 extrinsic apoptotic signaling pathway | IDA PMID:10588860 The phosphoprotein protein PEA-15 inhibits Fas- but increase... | ACCEPT | Summary: Casp8 mediates extrinsic apoptotic signaling. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Extrinsic apoptotic signaling is a correct and central Casp8 process supported by multiple mouse experimental rows; it is retained alongside the more specific death-domain-receptor descendant GO:0008625, matching the human CASP8 treatment. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097191 extrinsic apoptotic signaling pathway | IDA PMID:12011074 Relief of extrinsic pathway inhibition by the Bid-dependent ... | ACCEPT | Summary: Casp8 mediates extrinsic apoptotic signaling. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Extrinsic apoptotic signaling is a correct and central Casp8 process supported by multiple mouse experimental rows; it is retained alongside the more specific death-domain-receptor descendant GO:0008625, matching the human CASP8 treatment. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097191 extrinsic apoptotic signaling pathway | IDA PMID:12065591 Active caspase-8 translocates into the nucleus of apoptotic ... | ACCEPT | Summary: Casp8 mediates extrinsic apoptotic signaling. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Extrinsic apoptotic signaling is a correct and central Casp8 process supported by multiple mouse experimental rows; it is retained alongside the more specific death-domain-receptor descendant GO:0008625, matching the human CASP8 treatment. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097191 extrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Casp8 mediates extrinsic apoptotic signaling. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Extrinsic apoptotic signaling is a correct and central Casp8 process supported by multiple mouse experimental rows; it is retained alongside the more specific death-domain-receptor descendant GO:0008625, matching the human CASP8 treatment. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097191 extrinsic apoptotic signaling pathway | IGI PMID:22089168 TNF-induced necroptosis in L929 cells is tightly regulated b... | ACCEPT | Summary: Casp8 mediates extrinsic apoptotic signaling. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Extrinsic apoptotic signaling is a correct and central Casp8 process supported by multiple mouse experimental rows; it is retained alongside the more specific death-domain-receptor descendant GO:0008625, matching the human CASP8 treatment. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097191 extrinsic apoptotic signaling pathway | IGI PMID:22675671 Survival function of the FADD-CASPASE-8-cFLIP(L) complex. | ACCEPT | Summary: Casp8 mediates extrinsic apoptotic signaling. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Extrinsic apoptotic signaling is a correct and central Casp8 process supported by multiple mouse experimental rows; it is retained alongside the more specific death-domain-receptor descendant GO:0008625, matching the human CASP8 treatment. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097191 extrinsic apoptotic signaling pathway | IGI PMID:22675671 Survival function of the FADD-CASPASE-8-cFLIP(L) complex. | ACCEPT | Summary: Casp8 mediates extrinsic apoptotic signaling. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Extrinsic apoptotic signaling is a correct and central Casp8 process supported by multiple mouse experimental rows; it is retained alongside the more specific death-domain-receptor descendant GO:0008625, matching the human CASP8 treatment. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097191 extrinsic apoptotic signaling pathway | IMP PMID:31748744 Caspase-8 is the molecular switch for apoptosis, necroptosis... | ACCEPT | Summary: Casp8 mediates extrinsic apoptotic signaling. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Extrinsic apoptotic signaling is a correct and central Casp8 process supported by multiple mouse experimental rows; it is retained alongside the more specific death-domain-receptor descendant GO:0008625, matching the human CASP8 treatment. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097191 extrinsic apoptotic signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 mediates extrinsic apoptotic signaling. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. Extrinsic apoptotic signaling is a correct and central Casp8 process supported by multiple mouse experimental rows; it is retained alongside the more specific death-domain-receptor descendant GO:0008625, matching the human CASP8 treatment. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097194 execution phase of apoptosis | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Casp8 can contribute to the execution phase, but its core role is upstream initiation. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The execution-phase definition allows effector molecules other than executioner caspases; Casp8 directly cleaves structural and signaling substrates (e.g. plectin, BID) in addition to activating Casp3/Casp7. The experimental mouse rows are retained as non-core rather than recast, with GO:1900119 (accepted separately) capturing the dominant initiator role. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0097194 execution phase of apoptosis | IMP PMID:24813849 RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and ... | KEEP AS NON CORE | Summary: Casp8 can contribute to the execution phase, but its core role is upstream initiation. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The execution-phase definition allows effector molecules other than executioner caspases; Casp8 directly cleaves structural and signaling substrates (e.g. plectin, BID) in addition to activating Casp3/Casp7. The experimental mouse rows are retained as non-core rather than recast, with GO:1900119 (accepted separately) capturing the dominant initiator role. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0097194 execution phase of apoptosis | IMP PMID:24813850 RIPK1 blocks early postnatal lethality mediated by caspase-8... | KEEP AS NON CORE | Summary: Casp8 can contribute to the execution phase, but its core role is upstream initiation. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The execution-phase definition allows effector molecules other than executioner caspases; Casp8 directly cleaves structural and signaling substrates (e.g. plectin, BID) in addition to activating Casp3/Casp7. The experimental mouse rows are retained as non-core rather than recast, with GO:1900119 (accepted separately) capturing the dominant initiator role. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0097194 execution phase of apoptosis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Casp8 can contribute to the execution phase, but its core role is upstream initiation. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The execution-phase definition allows effector molecules other than executioner caspases; Casp8 directly cleaves structural and signaling substrates (e.g. plectin, BID) in addition to activating Casp3/Casp7. The experimental mouse rows are retained as non-core rather than recast, with GO:1900119 (accepted separately) capturing the dominant initiator role. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0097194 execution phase of apoptosis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Casp8 can contribute to the execution phase, but its core role is upstream initiation. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The execution-phase definition allows effector molecules other than executioner caspases; Casp8 directly cleaves structural and signaling substrates (e.g. plectin, BID) in addition to activating Casp3/Casp7. The experimental mouse rows are retained as non-core rather than recast, with GO:1900119 (accepted separately) capturing the dominant initiator role. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0097194 execution phase of apoptosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Casp8 can contribute to the execution phase, but its core role is upstream initiation. Reason: Ortholog audit 2026-10-12: aligned with human CASP8. The execution-phase definition allows effector molecules other than executioner caspases; Casp8 directly cleaves structural and signaling substrates (e.g. plectin, BID) in addition to activating Casp3/Casp7. The experimental mouse rows are retained as non-core rather than recast, with GO:1900119 (accepted separately) capturing the dominant initiator role. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:0097264 self proteolysis | IMP PMID:31511692 Cleavage of RIPK1 by caspase-8 is crucial for limiting apopt... | ACCEPT | Summary: Casp8 undergoes self-proteolysis after DISC- or signaling-complex-induced dimerization. Reason: Autoproteolytic processing releases or stabilizes the active Casp8 catalytic dimer from activation complexes. Supporting Evidence: PMID:31511692 cleavage of RIPK1 by caspase-8 is a mechanism for dismantling death-inducing complexes |
| GO:0097284 hepatocyte apoptotic process | IMP PMID:15322156 Caspase-8 serves both apoptotic and nonapoptotic roles. | KEEP AS NON CORE | Summary: This cell-type-specific apoptosis row is a contextual branch of Casp8 death signaling. Reason: The evidence supports Casp8-dependent apoptosis in a particular tissue or stimulus context, but the direct work is better captured by death-receptor signaling and substrate cleavage. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:0097342 ripoptosome | IEA GO_REF:0000107 | ACCEPT | Summary: Casp8 is a component of the RIPK1/FADD/cFLIP ripoptosome. Reason: The ripoptosome contains RIP1, FADD, caspase-8, caspase-10, and cFLIP isoforms and toggles between apoptosis and necroptosis. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0097342 ripoptosome | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 is a component of the RIPK1/FADD/cFLIP ripoptosome. Reason: The ripoptosome contains RIP1, FADD, caspase-8, caspase-10, and cFLIP isoforms and toggles between apoptosis and necroptosis. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0097342 ripoptosome | ISS GO_REF:0000024 | ACCEPT | Summary: Casp8 is a component of the RIPK1/FADD/cFLIP ripoptosome. Reason: The ripoptosome contains RIP1, FADD, caspase-8, caspase-10, and cFLIP isoforms and toggles between apoptosis and necroptosis. Supporting Evidence: PMID:21737330 It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms |
| GO:0140639 positive regulation of pyroptotic inflammatory response | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Casp8 can positively regulate pyroptotic inflammatory death through gasdermin cleavage. Reason: GSDMD cleavage is a direct inflammatory branch downstream of Casp8, but it is non-core relative to death-receptor apoptosis curation. Supporting Evidence: PMID:30361383 increased concentrations of mouse and human caspase-8 cleaved GSDMD |
| GO:1900119 positive regulation of execution phase of apoptosis | IDA PMID:9837723 Molecular cloning and identification of murine caspase-8. | ACCEPT | Summary: Casp8 proteolytically activates downstream caspases to positively regulate apoptotic execution. Reason: GO:1900119 is a regulatory term because Casp8 is not an executioner caspase itself, but direct procaspase processing by recombinant murine Casp8 is direct support for activation of the apoptotic execution phase. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:1900119 positive regulation of execution phase of apoptosis | IEA GO_REF:0000120 | ACCEPT | Summary: Casp8 proteolytically activates downstream caspases to positively regulate apoptotic execution. Reason: GO:1900119 correctly captures the regulatory consequence of Casp8-mediated procaspase cleavage without asserting that Casp8 is an execution-phase caspase. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:1900119 positive regulation of execution phase of apoptosis | IMP PMID:9729047 Targeted disruption of the mouse Caspase 8 gene ablates cell... | ACCEPT | Summary: Casp8 is required to induce death-receptor-triggered cell death and drive apoptotic execution. Reason: Casp8-null mice abolish cell death induction by TNF receptors, Fas/Apo1, and DR3; this supports the positive execution-phase regulation term rather than only generic protein maturation. Supporting Evidence: PMID:9729047 Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors |
| GO:1900119 positive regulation of execution phase of apoptosis | ISO GO_REF:0000119 | ACCEPT | Summary: Casp8 proteolytically activates downstream caspases to positively regulate apoptotic execution. Reason: GO:1900119 correctly captures the regulatory consequence of Casp8-mediated procaspase cleavage without asserting that Casp8 is an execution-phase caspase. Supporting Evidence: PMID:9837723 are processed by recombinant murine caspase-8 |
| GO:2001233 regulation of apoptotic signaling pathway | IGI PMID:15456877 Vhlh gene deletion induces Hif-1-mediated cell death in thym... | KEEP AS NON CORE | Summary: This cell-type-specific apoptosis row is a contextual branch of Casp8 death signaling. Reason: The evidence supports Casp8-dependent apoptosis in a particular tissue or stimulus context, but the direct work is better captured by death-receptor signaling and substrate cleavage. Supporting Evidence: PMID:15322156 participating in cell death induction by receptors of the TNF/nerve growth factor family |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IGI PMID:16183742 Apoptosis caused by p53-induced protein with death domain (P... | MARK AS OVER ANNOTATED | Summary: The PIDD/RAIDD genetic interaction does not support a positive Casp8 role in extrinsic apoptotic signaling. Reason: PIDD-induced apoptosis proceeded through RAIDD, caspase-2, and effector caspases rather than detectable Casp8 processing, so this row over-interprets the assay as Casp8 extrinsic signaling. Supporting Evidence: PMID:16183742 Processing of procaspase-8 and -9 was not detected in PIDD-expressing MEFs of either genotype |
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Download this section (compressed HTML)Q: Which mouse cytokine and pyroptotic inflammatory response rows should stay as flat Casp8 biological-process annotations rather than being represented only through GO-CAM substrate cleavage events?
Q: Should the Casp8/cFLIP survival checkpoint against necroptosis be represented with distinct RIPK1, CYLD, and RIPK3 cleavage activities once substrate-specific GO molecular functions exist?
Experiment: Compare endogenous catalytic-dead, DED-interface, and non-cleavable Casp8 knock-in alleles in mouse cells to separate FADD recruitment, RIPK1/CYLD cleavage, gasdermin cleavage, and apoptotic procaspase maturation.
Experiment: Use acute rescue of Casp8-null mouse macrophages and endothelial cells with wild-type versus cFLIP-binding-defective Casp8 to determine which developmental annotations reflect direct necroptosis-checkpoint activity.
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