CED-3 is the canonical C. elegans apoptotic caspase, a C14-family Asp-directed cysteine endopeptidase synthesized as an inactive zymogen and activated by CED-4-apoptosome-mediated dimerization and autoproteolysis. Active CED-3 cleaves execution substrates such as DCR-1, CED-8, CNT-1, FEM-1, and DRP-1 to drive apoptotic DNA fragmentation, phosphatidylserine exposure, organelle remodeling, and suppression of AKT survival signaling. CED-3 is also used in limited, non-apoptotic proteolysis, notably GSNL-1 activation during synapse pruning and LIN-14/LIN-28/DISL-2 cleavage during heterochronic developmental control; these nonlethal outputs reuse the caspase catalytic activity in restricted cellular contexts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004175 endopeptidase activity | IDA PMID:16208361 Structure of the CED-4-CED-9 complex provides insights into ... | MODIFY | Summary: CED-3 is a caspase-family cysteine endopeptidase; endopeptidase activity is correct but too broad. Reason: Use the caspase-specific cysteine-type endopeptidase term for CED-3 rather than the generic endopeptidase parent. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:10764728 The Caenorhabditis elegans sex determination protein FEM-1 i... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:18722182 Caenorhabditis elegans drp-1 and fis-2 regulate distinct cel... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:20223951 Caspase-dependent conversion of Dicer ribonuclease into a de... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:24225442 Caspase-mediated activation of Caenorhabditis elegans CED-8 ... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:25383666 Caspase-activated phosphoinositide binding by CNT-1 promotes... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:8631956 Protease activity of in vitro transcribed and translated Cae... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:8654923 The Caenorhabditis elegans cell-death protein CED-3 is a cys... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:9285582 Role of CED-4 in the activation of CED-3. | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:9384385 Caenorhabditis elegans CED-9 protein is a bifunctional cell-... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IEA GO_REF:0000002 | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:27723735 Regulation of CED-3 caspase localization and activation by C... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:9857046 Identification of multiple Caenorhabditis elegans caspases a... | ACCEPT | Summary: CED-3 enables cysteine-type endopeptidase activity as the C. elegans apoptotic caspase. Reason: Direct biochemical and substrate-cleavage studies, and conserved caspase-domain inference, all support this core molecular function. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0005515 protein binding | IPI PMID:10101135 C. elegans MAC-1, an essential member of the AAA family of A... | MODIFY | Summary: This row captures CED-4 apoptosome recruitment but uses the uninformative generic protein binding term. Reason: CED-3 binds CED-4 through apoptosome-recruitment contacts; replace generic protein binding with the more informative CARD domain binding molecular function. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:10101135 C. elegans MAC-1, an essential member of the AAA family of A... | REMOVE | Summary: This row captures a specific CED-3 interactor but uses the uninformative generic protein binding term. Reason: MAC-1 regulates the CED-4 apoptosome; this row does not capture a direct or informative CED-3 molecular function, so the generic GO:0005515 assertion should not be retained. |
| GO:0005515 protein binding | IPI PMID:11114722 The C. elegans orthologue ceBNIP3 interacts with CED-9 and C... | REMOVE | Summary: This row captures a specific CED-3 interactor but uses the uninformative generic protein binding term. Reason: DCT-1 acts upstream at mitochondria through CED-9 and CED-4; this context-specific genetic/regulatory connection is not a standalone CED-3 protein-binding function. |
| GO:0005515 protein binding | IPI PMID:16938876 Matefin/SUN-1 is a nuclear envelope receptor for CED-4 durin... | MODIFY | Summary: This row captures CED-4 apoptosome recruitment but uses the uninformative generic protein binding term. Reason: CED-3 binds CED-4 through apoptosome-recruitment contacts; replace generic protein binding with the more informative CARD domain binding molecular function. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:18776901 Inhibition of CED-3 zymogen activation and apoptosis in Caen... | REMOVE | Summary: This row captures a specific CED-3 interactor but uses the uninformative generic protein binding term. Reason: CSP-3 is a caspase-like inhibitor that binds and restrains the CED-3 zymogen; generic GO:0005515 does not add a specific CED-3 function beyond the accepted autoprocessing and inhibitor-regulation rows. |
| GO:0005515 protein binding | IPI PMID:18776901 Inhibition of CED-3 zymogen activation and apoptosis in Caen... | REMOVE | Summary: This row captures a specific CED-3 interactor but uses the uninformative generic protein binding term. Reason: CED-9 was assayed as a CED-3 substrate in this CSP-3 study; generic GO:0005515 adds no specific CED-3 function beyond its cysteine endopeptidase activity toward apoptotic substrates. |
| GO:0005515 protein binding | IPI PMID:19575016 Caenorhabditis elegans caspase homolog CSP-2 inhibits CED-3 ... | REMOVE | Summary: This row captures a specific CED-3 interactor but uses the uninformative generic protein binding term. Reason: CSP-2 is a germline caspase-like inhibitor that binds and restrains the CED-3 zymogen; this regulator interaction is not a standalone CED-3 protein-binding function. |
| GO:0005515 protein binding | IPI PMID:20434985 Crystal structure of the Caenorhabditis elegans apoptosome r... | MODIFY | Summary: This row captures CED-4 apoptosome recruitment but uses the uninformative generic protein binding term. Reason: CED-3 binds CED-4 through apoptosome-recruitment contacts; replace generic protein binding with the more informative CARD domain binding molecular function. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:24065769 Mechanistic insights into CED-4-mediated activation of CED-3... | MODIFY | Summary: This row captures CED-4 apoptosome recruitment but uses the uninformative generic protein binding term. Reason: CED-3 binds CED-4 through apoptosome-recruitment contacts; replace generic protein binding with the more informative CARD domain binding molecular function. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:27723735 Regulation of CED-3 caspase localization and activation by C... | REMOVE | Summary: This row captures a specific CED-3 interactor but uses the uninformative generic protein binding term. Reason: NPP-14 tethers CED-3 zymogen to the nuclear membrane and inhibits autoactivation; the CED-3 side is captured by its autoprocessing, protease-activity, and perinuclear-localization terms rather than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:9027312 Interaction of CED-4 with CED-3 and CED-9: a molecular frame... | MODIFY | Summary: This row captures CED-4 apoptosome recruitment but uses the uninformative generic protein binding term. Reason: CED-3 binds CED-4 through apoptosome-recruitment contacts; replace generic protein binding with the more informative CARD domain binding molecular function. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:9027312 Interaction of CED-4 with CED-3 and CED-9: a molecular frame... | REMOVE | Summary: This row captures a specific CED-3 interactor but uses the uninformative generic protein binding term. Reason: CED-9 was assayed as a CED-3 substrate or upstream death regulator; generic GO:0005515 adds no specific function beyond CED-3 protease activity and the ced-9/ced-4/ced-3 apoptosis pathway. |
| GO:0005515 protein binding | IPI PMID:9109415 Direct physical interaction between the Caenorhabditis elega... | MODIFY | Summary: The early CED-3-CED-4 interaction paper supports CARD-mediated adaptor binding, not generic protein binding. Reason: CED-3 and CED-4 prodomain/CARD-family regions mediate caspase adaptor recruitment, so CARD domain binding is the more informative molecular-function child. Proposed replacements: CARD domain binding Supporting Evidence: PMID:9109415 CED-4 was found to interact with CED-3. |
| GO:0005515 protein binding | IPI PMID:9261161 Interaction and regulation of the Caenorhabditis elegans dea... | MODIFY | Summary: This row captures CED-4 apoptosome recruitment but uses the uninformative generic protein binding term. Reason: CED-3 binds CED-4 through apoptosome-recruitment contacts; replace generic protein binding with the more informative CARD domain binding molecular function. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:9261161 Interaction and regulation of the Caenorhabditis elegans dea... | REMOVE | Summary: This row captures a specific CED-3 interactor but uses the uninformative generic protein binding term. Reason: CED-9 was assayed as a CED-3 substrate or upstream death regulator; generic GO:0005515 adds no specific function beyond CED-3 protease activity and the ced-9/ced-4/ced-3 apoptosis pathway. |
| GO:0005515 protein binding | IPI PMID:9651369 The death inhibitory molecules CED-9 and CED-4L use a common... | MODIFY | Summary: This row captures CED-4 apoptosome recruitment but uses the uninformative generic protein binding term. Reason: CED-3 binds CED-4 through apoptosome-recruitment contacts; replace generic protein binding with the more informative CARD domain binding molecular function. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:9651369 The death inhibitory molecules CED-9 and CED-4L use a common... | MODIFY | Summary: This row captures CED-4 apoptosome recruitment but uses the uninformative generic protein binding term. Reason: CED-3 binds CED-4 through apoptosome-recruitment contacts; replace generic protein binding with the more informative CARD domain binding molecular function. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:9824163 Regulation of apoptosis by a Caenorhabditis elegans BNIP3 ho... | REMOVE | Summary: This row captures a specific CED-3 interactor but uses the uninformative generic protein binding term. Reason: DCT-1/BNIP3 acts upstream at mitochondria through CED-9 and CED-4; this context-specific genetic or regulatory connection is not a standalone CED-3 protein-binding function. |
| GO:0005737 cytoplasm | EXP PMID:27723735 Regulation of CED-3 caspase localization and activation by C... | ACCEPT | Summary: CED-3 is cytoplasmic/perinuclear before apoptotic activation. Reason: NPP-14 and CED-4 regulation studies localize the CED-3 zymogen to cytoplasmic/perinuclear pools in germ cells and are consistent with conserved caspase cytosolic activity. Supporting Evidence: PMID:27723735 The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: CED-3 is cytoplasmic/perinuclear before apoptotic activation. Reason: NPP-14 and CED-4 regulation studies localize the CED-3 zymogen to cytoplasmic/perinuclear pools in germ cells and are consistent with conserved caspase cytosolic activity. Supporting Evidence: PMID:27723735 The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: CED-3 is cytoplasmic/perinuclear before apoptotic activation. Reason: NPP-14 and CED-4 regulation studies localize the CED-3 zymogen to cytoplasmic/perinuclear pools in germ cells and are consistent with conserved caspase cytosolic activity. Supporting Evidence: PMID:27723735 The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro. |
| GO:0005739 mitochondrion | IDA PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | KEEP AS NON CORE | Summary: CED-3 is observed near axonal mitochondria during its non-apoptotic synapse-pruning function. Reason: Mitochondrial localization is a real, local synapse-elimination context from the GSNL-1 pathway, but not the central apoptotic-execution localization. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CED-3 is observed near axonal mitochondria during its non-apoptotic synapse-pruning function. Reason: Mitochondrial localization is a real, local synapse-elimination context from the GSNL-1 pathway, but not the central apoptotic-execution localization. |
| GO:0006508 proteolysis | IBA GO_REF:0000033 | ACCEPT | Summary: CED-3 directly performs limited proteolysis of itself and downstream substrates. Reason: The broad proteolysis term is correct because CED-3 cleaves protein substrates in apoptosis and in non-apoptotic developmental contexts. Supporting Evidence: PMID:20223951 DCR-1 was cleaved by the CED-3 caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3' hydroxyl DNA breaks on chromosomes and promoted apoptosis. PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: CED-3 directly performs limited proteolysis of itself and downstream substrates. Reason: The broad proteolysis term is correct because CED-3 cleaves protein substrates in apoptosis and in non-apoptotic developmental contexts. Supporting Evidence: PMID:20223951 DCR-1 was cleaved by the CED-3 caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3' hydroxyl DNA breaks on chromosomes and promoted apoptosis. PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0006508 proteolysis | IMP PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | ACCEPT | Summary: CED-3 directly performs limited proteolysis of itself and downstream substrates. Reason: The broad proteolysis term is correct because CED-3 cleaves protein substrates in apoptosis and in non-apoptotic developmental contexts. Supporting Evidence: PMID:20223951 DCR-1 was cleaved by the CED-3 caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3' hydroxyl DNA breaks on chromosomes and promoted apoptosis. PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0006915 apoptotic process | IBA GO_REF:0000033 | MODIFY | Summary: CED-3 participates in apoptotic execution rather than only a generic apoptotic process. Reason: CED-3 is the cell-killing caspase that executes the worm canonical apoptosis pathway after activation by CED-4; the execution-phase child is the better process term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000047947 Β· caspase-family PAINT node SUPPORTS TRANSFER The family inference supports apoptotic caspase function, but CED-3 should be curated to the execution phase rather than only the top-level apoptotic process parent. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0006915 apoptotic process | IGI PMID:10101135 C. elegans MAC-1, an essential member of the AAA family of A... | MODIFY | Summary: CED-3 participates in apoptotic execution rather than only a generic apoptotic process. Reason: CED-3 is the cell-killing caspase that executes the worm canonical apoptosis pathway after activation by CED-4; the execution-phase child is the better process term. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0006915 apoptotic process | IGI PMID:10101135 C. elegans MAC-1, an essential member of the AAA family of A... | MODIFY | Summary: CED-3 participates in apoptotic execution rather than only a generic apoptotic process. Reason: CED-3 is the cell-killing caspase that executes the worm canonical apoptosis pathway after activation by CED-4; the execution-phase child is the better process term. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0006915 apoptotic process | IMP PMID:11226309 Programmed cell death mediated by ced-3 and ced-4 protects C... | MODIFY | Summary: CED-3 participates in apoptotic execution rather than only a generic apoptotic process. Reason: CED-3 is the cell-killing caspase that executes the worm canonical apoptosis pathway after activation by CED-4; the execution-phase child is the better process term. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0006915 apoptotic process | IMP PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | MODIFY | Summary: CED-3 participates in apoptotic execution rather than only a generic apoptotic process. Reason: CED-3 is the cell-killing caspase that executes the worm canonical apoptosis pathway after activation by CED-4; the execution-phase child is the better process term. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0006915 apoptotic process | IMP PMID:27723735 Regulation of CED-3 caspase localization and activation by C... | MODIFY | Summary: CED-3 participates in apoptotic execution rather than only a generic apoptotic process. Reason: CED-3 is the cell-killing caspase that executes the worm canonical apoptosis pathway after activation by CED-4; the execution-phase child is the better process term. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0006915 apoptotic process | IMP PMID:3955651 Genetic control of programmed cell death in the nematode C. ... | MODIFY | Summary: CED-3 participates in apoptotic execution rather than only a generic apoptotic process. Reason: CED-3 is the cell-killing caspase that executes the worm canonical apoptosis pathway after activation by CED-4; the execution-phase child is the better process term. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0006915 apoptotic process | IMP PMID:9604928 The C. elegans protein EGL-1 is required for programmed cell... | MODIFY | Summary: CED-3 participates in apoptotic execution rather than only a generic apoptotic process. Reason: CED-3 is the cell-killing caspase that executes the worm canonical apoptosis pathway after activation by CED-4; the execution-phase child is the better process term. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0008047 enzyme activator activity | IBA GO_REF:0000033 | REMOVE | Summary: Proteolytic cleavage of substrates should not be represented as a separate enzyme activator molecular function. Reason: CED-3 is the cysteine endopeptidase that cleaves protein substrates; downstream activation of substrates such as DCR-1, CED-8, or GSNL-1 is a consequence of proteolysis, not an independent enzyme activator activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002235080 Β· caspase-family PAINT node SUPPORTS SOURCE BUT NOT TARGET The node captures caspase-mediated cleavage but scopes it as a regulatory MF rather than CED-3 protease activity. |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000002 | MODIFY | Summary: Cysteine-type peptidase activity is true but less specific than cysteine-type endopeptidase activity. Reason: The mapped InterPro family is a C14 caspase endopeptidase family; GO:0004197 captures the activity more precisely. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR015917 Β· peptidase C14 caspase domain SUPPORTS TRANSFER The InterPro signature supports a caspase endopeptidase but maps to an avoidably broad cysteine-type peptidase term. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0008303 caspase complex | IDA PMID:10101135 C. elegans MAC-1, an essential member of the AAA family of A... | ACCEPT | Summary: CED-3 binds the octameric CED-4 apoptosome to form the CED-3 activation complex. Reason: Structural and biochemical data show that CED-4 recruits CED-3 zymogens and retains processed CED-3 as a CED-4-CED-3 holoenzyme. Supporting Evidence: PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0008303 caspase complex | IDA PMID:24065769 Mechanistic insights into CED-4-mediated activation of CED-3... | ACCEPT | Summary: CED-3 binds the octameric CED-4 apoptosome to form the CED-3 activation complex. Reason: Structural and biochemical data show that CED-4 recruits CED-3 zymogens and retains processed CED-3 as a CED-4-CED-3 holoenzyme. Supporting Evidence: PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0008303 caspase complex | IMP PMID:24065769 Mechanistic insights into CED-4-mediated activation of CED-3... | ACCEPT | Summary: CED-3 binds the octameric CED-4 apoptosome to form the CED-3 activation complex. Reason: Structural and biochemical data show that CED-4 recruits CED-3 zymogens and retains processed CED-3 as a CED-4-CED-3 holoenzyme. Supporting Evidence: PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process | IMP PMID:24065769 Mechanistic insights into CED-4-mediated activation of CED-3... | MODIFY | Summary: The CED-4-mediated activation paper supports apoptosome-stimulated CED-3 autoprocessing. Reason: Within the CED-4 apoptosome, CED-3 zymogens mature by trans-autoprocessing; replace the broad activator molecular function with the directly supported protein autoprocessing process. Proposed replacements: protein autoprocessing |
| GO:0009792 embryo development ending in birth or egg hatching | IGI PMID:21502138 Shared developmental roles and transcriptional control of au... | UNDECIDED | Summary: The autophagy/apoptosis developmental interaction is too distal for a confident ced-3 embryo-development assertion from cached evidence. Reason: The row derives from an abstract-only genetic interaction around ATF-2, autophagy, and apoptosis; leave the exact broad embryo-development process for full-text worm curation. |
| GO:0009792 embryo development ending in birth or egg hatching | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | UNDECIDED | Summary: The miRNA enhancer paper supports CED-3 cleavage of developmental regulators but not this exact embryo-development endpoint from the cached abstract. Reason: The source establishes non-apoptotic CED-3 proteolysis of heterochronic/miRNA targets; keep the broad embryogenesis row undecided until full evidence for embryo development ending in hatching is checked. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0010954 positive regulation of protein processing | IMP PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | MODIFY | Summary: The GSNL-1 row should describe synapse pruning rather than positive regulation of protein processing. Reason: CED-3 cleaves GSNL-1 in the RME-neuron pathway that removes transient presynaptic clusters; the biological process is synapse pruning, with GSNL-1 processing as the molecular step. Proposed replacements: positive regulation of synapse pruning Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0012501 programmed cell death | IMP PMID:17237514 DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-fi... | MODIFY | Summary: Programmed cell death is too broad for the canonical CED-3 executioner role. Reason: CED-3 is specifically the executor caspase downstream of the egl-1/ced-9/ced-4 activation module, so execution phase of apoptosis is the more precise term. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0016020 membrane | IDA PMID:9651369 The death inhibitory molecules CED-9 and CED-4L use a common... | UNDECIDED | Summary: The cached CED-4L/CED-9 abstract supports CED-3 processing control but does not establish CED-3 membrane localization. Reason: CED-9 and CED-4 are membrane-associated regulators, but the abstract-only CED-4L study does not show that CED-3 itself is located at a membrane. |
| GO:0016540 protein autoprocessing | IDA PMID:16208361 Structure of the CED-4-CED-9 complex provides insights into ... | ACCEPT | Summary: CED-3 zymogen activation uses autocatalytic proteolytic processing. Reason: Biochemical reconstitution and inhibitor studies support CED-3 self-processing, which is accelerated by the CED-4 apoptosome and restrained by CSP-2, CSP-3, or NPP-14. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0016540 protein autoprocessing | IDA PMID:18776901 Inhibition of CED-3 zymogen activation and apoptosis in Caen... | ACCEPT | Summary: CED-3 zymogen activation uses autocatalytic proteolytic processing. Reason: Biochemical reconstitution and inhibitor studies support CED-3 self-processing, which is accelerated by the CED-4 apoptosome and restrained by CSP-2, CSP-3, or NPP-14. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0016540 protein autoprocessing | IDA PMID:19575016 Caenorhabditis elegans caspase homolog CSP-2 inhibits CED-3 ... | ACCEPT | Summary: CED-3 zymogen activation uses autocatalytic proteolytic processing. Reason: Biochemical reconstitution and inhibitor studies support CED-3 self-processing, which is accelerated by the CED-4 apoptosome and restrained by CSP-2, CSP-3, or NPP-14. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0016540 protein autoprocessing | IDA PMID:9857046 Identification of multiple Caenorhabditis elegans caspases a... | ACCEPT | Summary: CED-3 zymogen activation uses autocatalytic proteolytic processing. Reason: Biochemical reconstitution and inhibitor studies support CED-3 self-processing, which is accelerated by the CED-4 apoptosome and restrained by CSP-2, CSP-3, or NPP-14. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0016540 protein autoprocessing | IMP PMID:24065769 Mechanistic insights into CED-4-mediated activation of CED-3... | ACCEPT | Summary: CED-3 zymogen activation uses autocatalytic proteolytic processing. Reason: Biochemical reconstitution and inhibitor studies support CED-3 self-processing, which is accelerated by the CED-4 apoptosome and restrained by CSP-2, CSP-3, or NPP-14. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0016540 protein autoprocessing | IMP PMID:27723735 Regulation of CED-3 caspase localization and activation by C... | ACCEPT | Summary: CED-3 zymogen activation uses autocatalytic proteolytic processing. Reason: Biochemical reconstitution and inhibitor studies support CED-3 self-processing, which is accelerated by the CED-4 apoptosome and restrained by CSP-2, CSP-3, or NPP-14. Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0030042 actin filament depolymerization | IMP PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | MODIFY | Summary: CED-3 promotes actin disassembly indirectly by proteolytically activating GSNL-1 during synapse pruning. Reason: GSNL-1 is the actin-severing effector; CED-3 acts upstream by cleaving GSNL-1, so positive regulation of synapse pruning is the more faithful process term for this row. Proposed replacements: positive regulation of synapse pruning Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0030155 regulation of cell adhesion | IMP PMID:22801495 Programmed elimination of cells by caspase-independent cell ... | MARK AS OVER ANNOTATED | Summary: The cell-adhesion phenotype belongs to a caspase-independent shedding pathway in cells that survive ced-3 loss. Reason: The paper identifies PAR-4/STRD-1/MOP-25 and PIG-1 as the shedding-cell detachment machinery; it does not place CED-3 as a direct regulator of cell adhesion. Supporting Evidence: PMID:22801495 PIG-1 promotes shed-cell detachment by preventing the cell-surface expression of cell-adhesion molecules. |
| GO:0030163 protein catabolic process | IDA PMID:10764728 The Caenorhabditis elegans sex determination protein FEM-1 i... | MODIFY | Summary: Protein catabolic process is too broad and degradative for limited CED-3 substrate cleavage. Reason: CED-3 performs limited caspase proteolysis rather than bulk protein catabolism, so GO:0006508 proteolysis is the better process parent. Proposed replacements: proteolysis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0030163 protein catabolic process | IDA PMID:8631956 Protease activity of in vitro transcribed and translated Cae... | MODIFY | Summary: Protein catabolic process is too broad and degradative for limited CED-3 substrate cleavage. Reason: CED-3 performs limited caspase proteolysis rather than bulk protein catabolism, so GO:0006508 proteolysis is the better process parent. Proposed replacements: proteolysis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0030163 protein catabolic process | IDA PMID:8654923 The Caenorhabditis elegans cell-death protein CED-3 is a cys... | MODIFY | Summary: Protein catabolic process is too broad and degradative for limited CED-3 substrate cleavage. Reason: CED-3 performs limited caspase proteolysis rather than bulk protein catabolism, so GO:0006508 proteolysis is the better process parent. Proposed replacements: proteolysis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0030163 protein catabolic process | IDA PMID:9285582 Role of CED-4 in the activation of CED-3. | MODIFY | Summary: Protein catabolic process is too broad and degradative for limited CED-3 substrate cleavage. Reason: CED-3 performs limited caspase proteolysis rather than bulk protein catabolism, so GO:0006508 proteolysis is the better process parent. Proposed replacements: proteolysis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0031647 regulation of protein stability | IGI PMID:24285704 Maintenance of muscle myosin levels in adult C. elegans requ... | UNDECIDED | Summary: The muscle-myosin phenotype is caspase dependent but the cached abstract does not show the direct CED-3 substrate or stability step. Reason: The study connects adult myosin depletion in bet-1;sumo-1 mutants to caspase activity and MEK signaling, but this source does not justify a direct CED-3 regulation-of-protein-stability annotation. |
| GO:0031965 nuclear membrane | EXP PMID:27723735 Regulation of CED-3 caspase localization and activation by C... | ACCEPT | Summary: CED-3 localizes to the nuclear membrane/perinuclear region in germ cells. Reason: The NPP-14 study directly places the CED-3 zymogen at the nuclear membrane and shows that this localization restrains autoactivation. Supporting Evidence: PMID:27723735 The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro. |
| GO:0031965 nuclear membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear-membrane localization is a real but context-specific regulatory localization for the CED-3 zymogen. Reason: The UniProt SubCell transfer is consistent with the NPP-14 germline study, which directly localizes the CED-3 zymogen to the nuclear membrane/perinuclear region and connects that pool to zymogen restraint. Supporting Evidence: PMID:27723735 The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro. |
| GO:0040012 regulation of locomotion | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | UNDECIDED | Summary: The miRNA enhancer study supports non-apoptotic developmental proteolysis but not this exact organismal endpoint from cached evidence. Reason: CED-3 cleavage of LIN-14, LIN-28, and DISL-2 plausibly affects locomotion and vulval-development phenotypes in sensitized animals, but this exact row needs the full genetic context checked. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0040028 regulation of vulval development | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | UNDECIDED | Summary: The miRNA enhancer study supports non-apoptotic developmental proteolysis but not this exact organismal endpoint from cached evidence. Reason: CED-3 cleavage of LIN-14, LIN-28, and DISL-2 plausibly affects locomotion and vulval-development phenotypes in sensitized animals, but this exact row needs the full genetic context checked. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0040034 regulation of development, heterochronic | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | KEEP AS NON CORE | Summary: CED-3 has a non-apoptotic role in developmental timing and cell-fate robustness through limited proteolysis of miRNA pathway targets. Reason: The miRNA enhancer screen supports a direct CED-3 cleavage pathway for LIN-14, LIN-28, and DISL-2, but these larval patterning effects are secondary to the apoptotic caspase core. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0040034 regulation of development, heterochronic | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | KEEP AS NON CORE | Summary: CED-3 has a non-apoptotic role in developmental timing and cell-fate robustness through limited proteolysis of miRNA pathway targets. Reason: The miRNA enhancer screen supports a direct CED-3 cleavage pathway for LIN-14, LIN-28, and DISL-2, but these larval patterning effects are secondary to the apoptotic caspase core. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0040034 regulation of development, heterochronic | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | KEEP AS NON CORE | Summary: CED-3 has a non-apoptotic role in developmental timing and cell-fate robustness through limited proteolysis of miRNA pathway targets. Reason: The miRNA enhancer screen supports a direct CED-3 cleavage pathway for LIN-14, LIN-28, and DISL-2, but these larval patterning effects are secondary to the apoptotic caspase core. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0040034 regulation of development, heterochronic | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | KEEP AS NON CORE | Summary: CED-3 has a non-apoptotic role in developmental timing and cell-fate robustness through limited proteolysis of miRNA pathway targets. Reason: The miRNA enhancer screen supports a direct CED-3 cleavage pathway for LIN-14, LIN-28, and DISL-2, but these larval patterning effects are secondary to the apoptotic caspase core. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0042659 regulation of cell fate specification | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | KEEP AS NON CORE | Summary: CED-3 has a non-apoptotic role in developmental timing and cell-fate robustness through limited proteolysis of miRNA pathway targets. Reason: The miRNA enhancer screen supports a direct CED-3 cleavage pathway for LIN-14, LIN-28, and DISL-2, but these larval patterning effects are secondary to the apoptotic caspase core. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0042659 regulation of cell fate specification | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | KEEP AS NON CORE | Summary: CED-3 has a non-apoptotic role in developmental timing and cell-fate robustness through limited proteolysis of miRNA pathway targets. Reason: The miRNA enhancer screen supports a direct CED-3 cleavage pathway for LIN-14, LIN-28, and DISL-2, but these larval patterning effects are secondary to the apoptotic caspase core. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0042659 regulation of cell fate specification | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | KEEP AS NON CORE | Summary: CED-3 has a non-apoptotic role in developmental timing and cell-fate robustness through limited proteolysis of miRNA pathway targets. Reason: The miRNA enhancer screen supports a direct CED-3 cleavage pathway for LIN-14, LIN-28, and DISL-2, but these larval patterning effects are secondary to the apoptotic caspase core. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0042659 regulation of cell fate specification | IGI PMID:25432023 CED-3 caspase acts with miRNAs to regulate non-apoptotic gen... | KEEP AS NON CORE | Summary: CED-3 has a non-apoptotic role in developmental timing and cell-fate robustness through limited proteolysis of miRNA pathway targets. Reason: The miRNA enhancer screen supports a direct CED-3 cleavage pathway for LIN-14, LIN-28, and DISL-2, but these larval patterning effects are secondary to the apoptotic caspase core. Supporting Evidence: PMID:25432023 We provide evidence for a non-apoptotic function of CED-3 caspase that regulates multiple developmental events through proteolytic inactivation. |
| GO:0042802 identical protein binding | IPI PMID:18776901 Inhibition of CED-3 zymogen activation and apoptosis in Caen... | ACCEPT | Summary: CED-3 self-association is part of its apoptosome-facilitated activation mechanism. Reason: The CED-4 apoptosome recruits two CED-3 zymogens and facilitates dimerization and autocatalytic maturation, consistent with direct CED-3 self-association during activation. Supporting Evidence: PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0042802 identical protein binding | IPI PMID:20434985 Crystal structure of the Caenorhabditis elegans apoptosome r... | ACCEPT | Summary: CED-3 self-association is part of its apoptosome-facilitated activation mechanism. Reason: The CED-4 apoptosome recruits two CED-3 zymogens and facilitates dimerization and autocatalytic maturation, consistent with direct CED-3 self-association during activation. Supporting Evidence: PMID:24065769 CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | MODIFY | Summary: A generic regulation-of-apoptosis IEA row should be narrowed to CED-3 execution. Reason: The caspase-family InterPro signature supports apoptotic caspase function, but CED-3 is the executioner protease rather than a signless generic apoptosis regulator. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR001315 Β· peptidase C14A caspase catalytic subunit p20 SUPPORTS TRANSFER The electronic domain mapping supports a caspase process annotation but used a broad regulatory parent. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:0043025 neuronal cell body | IDA PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | KEEP AS NON CORE | Summary: This neuronal compartment is part of the local, non-apoptotic CED-3 synapse-pruning pathway. Reason: CED-3 localizes with axonal mitochondria and presynaptic material in RME neurons during GSNL-1-dependent synapse elimination; this is real but separate from bulk apoptotic execution. Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0043204 perikaryon | EXP PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | KEEP AS NON CORE | Summary: This neuronal compartment is part of the local, non-apoptotic CED-3 synapse-pruning pathway. Reason: CED-3 localizes with axonal mitochondria and presynaptic material in RME neurons during GSNL-1-dependent synapse elimination; this is real but separate from bulk apoptotic execution. Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: This neuronal compartment is part of the local, non-apoptotic CED-3 synapse-pruning pathway. Reason: CED-3 localizes with axonal mitochondria and presynaptic material in RME neurons during GSNL-1-dependent synapse elimination; this is real but separate from bulk apoptotic execution. Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0043525 positive regulation of neuron apoptotic process | IBA GO_REF:0000033 | MODIFY | Summary: A neuron-apoptosis PAINT parent should be represented as CED-3 execution rather than a cell-type-specific regulatory child. Reason: CED-3 is the conserved apoptotic caspase and certainly executes deaths in neuronal lineages, but the direct inherited process is execution phase of apoptosis rather than positive regulation of neuron apoptotic process. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000047947 Β· caspase-family PAINT node SUPPORTS TRANSFER The node supports inherited apoptotic caspase biology but the neuron-specific regulatory child is less direct than CED-3 execution. Proposed replacements: execution phase of apoptosis |
| GO:0043525 positive regulation of neuron apoptotic process | IMP PMID:23721876 The Nrf2/SKN-1-dependent glutathione S-transferase Ο homolog... | UNDECIDED | Summary: The manganese row is an abstract-supported dopaminergic-neurodegeneration phenotype whose exact apoptotic scope is not fully resolvable locally. Reason: The abstract says Mn-induced DA neuron degeneration is largely dependent on CED-3 and CSP-1, but the cached source is insufficient to decide whether this is canonical neuron apoptosis or a stress-degeneration endpoint. |
| GO:0045202 synapse | EXP PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | KEEP AS NON CORE | Summary: This neuronal compartment is part of the local, non-apoptotic CED-3 synapse-pruning pathway. Reason: CED-3 localizes with axonal mitochondria and presynaptic material in RME neurons during GSNL-1-dependent synapse elimination; this is real but separate from bulk apoptotic execution. Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0045202 synapse | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: This neuronal compartment is part of the local, non-apoptotic CED-3 synapse-pruning pathway. Reason: CED-3 localizes with axonal mitochondria and presynaptic material in RME neurons during GSNL-1-dependent synapse elimination; this is real but separate from bulk apoptotic execution. Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0046716 muscle cell cellular homeostasis | IGI PMID:24285704 Maintenance of muscle myosin levels in adult C. elegans requ... | UNDECIDED | Summary: The adult muscle-homeostasis row is a distal myosin-maintenance phenotype rather than a direct CED-3 function from cached evidence. Reason: The cached abstract reports a caspase-dependent mechanism in bet-1;sumo-1 adults, but does not identify a CED-3 substrate or prove that CED-3 directly executes muscle-cell homeostasis. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:20970339 Meiotic errors activate checkpoints that improve gamete qual... | KEEP AS NON CORE | Summary: CED-3 zymogen perinuclear localization in germ cells is mediated by NPP-14. Reason: The localization is direct and well supported, but it is a restraint mechanism for zymogen activation in germ cells rather than the core protease function. Supporting Evidence: PMID:27723735 The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CED-3 zymogen perinuclear localization in germ cells is mediated by NPP-14. Reason: The localization is direct and well supported, but it is a restraint mechanism for zymogen activation in germ cells rather than the core protease function. Supporting Evidence: PMID:27723735 The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro. |
| GO:0048471 perinuclear region of cytoplasm | IMP PMID:27723735 Regulation of CED-3 caspase localization and activation by C... | KEEP AS NON CORE | Summary: CED-3 zymogen perinuclear localization in germ cells is mediated by NPP-14. Reason: The localization is direct and well supported, but it is a restraint mechanism for zymogen activation in germ cells rather than the core protease function. Supporting Evidence: PMID:27723735 The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro. |
| GO:0050807 regulation of synapse organization | IGI PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | KEEP AS NON CORE | Summary: CED-3 cleaves GSNL-1 to promote elimination of transient presynaptic components. Reason: This is a direct non-apoptotic proteolytic output of CED-3 in developing neurons, but it is separable from canonical apoptosis. Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:11226309 Programmed cell death mediated by ced-3 and ced-4 protects C... | MARK AS OVER ANNOTATED | Summary: Salmonella-induced germline death and survival are host-level outputs of CED-3/CED-4 apoptosis. Reason: The study shows that pathogen-induced germline cell death and Salmonella survival require ced-3 and ced-4, but CED-3 is executing apoptosis rather than directly mediating a bacterium-specific defense response. |
| GO:0097194 execution phase of apoptosis | IBA GO_REF:0000033 | ACCEPT | Summary: CED-3 substrate cleavage is a direct execution-phase event in worm apoptosis. Reason: CED-3 cleaves execution substrates such as DCR-1, CED-8, CNT-1, and DRP-1 to drive DNA fragmentation, phosphatidylserine exposure, AKT suppression, and organelle/corpse remodeling. Supporting Evidence: PMID:20223951 DCR-1 was cleaved by the CED-3 caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3' hydroxyl DNA breaks on chromosomes and promoted apoptosis. PMID:24225442 Here we report that CED-8, a Caenorhabditis elegans protein implicated in controlling the kinetics of apoptosis and a homologue of the XK family proteins, is a substrate of the CED-3 caspase. PMID:25383666 In this study, we report a new CED-3 substrate, CNT-1, whose cleavage by CED-3 activates an N-terminal cleavage product, truncated CNT-1 (tCNT-1), that promotes apoptosis by suppressing the AKT pro-survival activity. |
| GO:0097194 execution phase of apoptosis | IDA PMID:18722182 Caenorhabditis elegans drp-1 and fis-2 regulate distinct cel... | ACCEPT | Summary: CED-3 substrate cleavage is a direct execution-phase event in worm apoptosis. Reason: CED-3 cleaves execution substrates such as DCR-1, CED-8, CNT-1, and DRP-1 to drive DNA fragmentation, phosphatidylserine exposure, AKT suppression, and organelle/corpse remodeling. Supporting Evidence: PMID:20223951 DCR-1 was cleaved by the CED-3 caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3' hydroxyl DNA breaks on chromosomes and promoted apoptosis. PMID:24225442 Here we report that CED-8, a Caenorhabditis elegans protein implicated in controlling the kinetics of apoptosis and a homologue of the XK family proteins, is a substrate of the CED-3 caspase. PMID:25383666 In this study, we report a new CED-3 substrate, CNT-1, whose cleavage by CED-3 activates an N-terminal cleavage product, truncated CNT-1 (tCNT-1), that promotes apoptosis by suppressing the AKT pro-survival activity. |
| GO:0097194 execution phase of apoptosis | IDA PMID:20223951 Caspase-dependent conversion of Dicer ribonuclease into a de... | ACCEPT | Summary: CED-3 substrate cleavage is a direct execution-phase event in worm apoptosis. Reason: CED-3 cleaves execution substrates such as DCR-1, CED-8, CNT-1, and DRP-1 to drive DNA fragmentation, phosphatidylserine exposure, AKT suppression, and organelle/corpse remodeling. Supporting Evidence: PMID:20223951 DCR-1 was cleaved by the CED-3 caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3' hydroxyl DNA breaks on chromosomes and promoted apoptosis. PMID:24225442 Here we report that CED-8, a Caenorhabditis elegans protein implicated in controlling the kinetics of apoptosis and a homologue of the XK family proteins, is a substrate of the CED-3 caspase. PMID:25383666 In this study, we report a new CED-3 substrate, CNT-1, whose cleavage by CED-3 activates an N-terminal cleavage product, truncated CNT-1 (tCNT-1), that promotes apoptosis by suppressing the AKT pro-survival activity. |
| GO:0097194 execution phase of apoptosis | IDA PMID:24225442 Caspase-mediated activation of Caenorhabditis elegans CED-8 ... | ACCEPT | Summary: CED-3 substrate cleavage is a direct execution-phase event in worm apoptosis. Reason: CED-3 cleaves execution substrates such as DCR-1, CED-8, CNT-1, and DRP-1 to drive DNA fragmentation, phosphatidylserine exposure, AKT suppression, and organelle/corpse remodeling. Supporting Evidence: PMID:20223951 DCR-1 was cleaved by the CED-3 caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3' hydroxyl DNA breaks on chromosomes and promoted apoptosis. PMID:24225442 Here we report that CED-8, a Caenorhabditis elegans protein implicated in controlling the kinetics of apoptosis and a homologue of the XK family proteins, is a substrate of the CED-3 caspase. PMID:25383666 In this study, we report a new CED-3 substrate, CNT-1, whose cleavage by CED-3 activates an N-terminal cleavage product, truncated CNT-1 (tCNT-1), that promotes apoptosis by suppressing the AKT pro-survival activity. |
| GO:0098793 presynapse | IDA PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | KEEP AS NON CORE | Summary: This neuronal compartment is part of the local, non-apoptotic CED-3 synapse-pruning pathway. Reason: CED-3 localizes with axonal mitochondria and presynaptic material in RME neurons during GSNL-1-dependent synapse elimination; this is real but separate from bulk apoptotic execution. Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:0140608 cysteine-type endopeptidase activator activity | IDA PMID:19575016 Caenorhabditis elegans caspase homolog CSP-2 inhibits CED-3 ... | MODIFY | Summary: The CSP-2 paper supports CED-3 zymogen autoprocessing and CSP-mediated inhibition. Reason: PMID:19575016 directly assayed CED-3 zymogen autoprocessing and its inhibition by CSP-2; replace this broad activator molecular function with GO:0016540 protein autoprocessing. Proposed replacements: protein autoprocessing Supporting Evidence: PMID:19575016 CSP-2 associates with the CED-3 zymogen and inhibits its autoactivation |
| GO:0140608 cysteine-type endopeptidase activator activity | IMP PMID:18776901 Inhibition of CED-3 zymogen activation and apoptosis in Caen... | MODIFY | Summary: The CSP-3 paper supports CED-3 zymogen autoprocessing and CSP-mediated inhibition. Reason: PMID:18776901 directly assayed CED-3 zymogen autoprocessing and its inhibition by CSP-3; replace this broad activator molecular function with GO:0016540 protein autoprocessing. Proposed replacements: protein autoprocessing Supporting Evidence: PMID:18776901 CSP-3 associates with the large subunit of the CED-3 zymogen and inhibits zymogen autoactivation. |
| GO:1900118 negative regulation of execution phase of apoptosis | IMP PMID:10101135 C. elegans MAC-1, an essential member of the AAA family of A... | REMOVE | Summary: Negative regulation of execution is the role of MAC-1/CSP/NPP-14-like inhibitors, not the inhibited CED-3 protease. Reason: CED-3 is the executioner caspase. Its presence in inhibitory complexes does not mean CED-3 itself negatively regulates execution phase. |
| GO:1902742 apoptotic process involved in development | IMP PMID:22801495 Programmed elimination of cells by caspase-independent cell ... | KEEP AS NON CORE | Summary: The caspase-independent cell-shedding paper is weak support for an already established CED-3 developmental-apoptosis role. Reason: PMID:22801495 uses ced-3 loss to expose PAR-4/PIG-1-dependent shedding as a backup route, so it is weak and redundant support for GO:1902742 rather than evidence that the term itself overshoots CED-3. Supporting Evidence: PMID:22801495 Here we identify a mechanism of cell extrusion that is caspase independent and that can eliminate a subset of the Caenorhabditis elegans cells programmed to die during embryonic development. |
| GO:1904747 positive regulation of apoptotic process involved in development | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1904747 positive regulation of apoptotic process involved in development | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1904747 positive regulation of apoptotic process involved in development | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1904747 positive regulation of apoptotic process involved in development | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1904747 positive regulation of apoptotic process involved in development | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1904747 positive regulation of apoptotic process involved in development | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1904747 positive regulation of apoptotic process involved in development | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1904747 positive regulation of apoptotic process involved in development | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1904747 positive regulation of apoptotic process involved in development | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1904747 positive regulation of apoptotic process involved in development | IMP PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: The CSP-1 combinatorial genetics still places CED-3 in canonical apoptotic execution. Reason: The paper distinguishes CSP-1 and caspase-independent branches from the canonical pathway involving CED-3 activation; CED-3 should be curated to execution phase rather than positive regulation of developmental apoptosis. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:23505386 We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. |
| GO:1905803 negative regulation of cellular response to manganese ion | IMP PMID:23721876 The Nrf2/SKN-1-dependent glutathione S-transferase Ο homolog... | UNDECIDED | Summary: CED-3/CSP-1 dependence in manganese-induced DA neuron death is a stress phenotype whose direct process remains unclear. Reason: The abstract supports a caspase-dependent manganese neurodegeneration phenotype but does not establish that CED-3 directly regulates the cellular manganese response. |
| GO:1905808 positive regulation of synapse pruning | IGI PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | KEEP AS NON CORE | Summary: CED-3 cleaves GSNL-1 to promote elimination of transient presynaptic components. Reason: This is a direct non-apoptotic proteolytic output of CED-3 in developing neurons, but it is separable from canonical apoptosis. Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:1905808 positive regulation of synapse pruning | IMP PMID:26074078 The Cell Death Pathway Regulates Synapse Elimination through... | KEEP AS NON CORE | Summary: CED-3 cleaves GSNL-1 to promote elimination of transient presynaptic components. Reason: This is a direct non-apoptotic proteolytic output of CED-3 in developing neurons, but it is separable from canonical apoptosis. Supporting Evidence: PMID:26074078 Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. |
| GO:1905845 positive regulation of cellular response to gamma radiation | IGI PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: Gamma-radiation-induced germline apoptosis ultimately uses CED-3 execution. Reason: The gamma-radiation row is a stimulus endpoint; the direct conserved role of CED-3 is the execution phase once developmental or damage signals activate the canonical pathway. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
| GO:1905845 positive regulation of cellular response to gamma radiation | IMP PMID:23505386 Both the caspase CSP-1 and a caspase-independent pathway pro... | MODIFY | Summary: Gamma-radiation-induced germline apoptosis ultimately uses CED-3 execution. Reason: The gamma-radiation row is a stimulus endpoint; the direct conserved role of CED-3 is the execution phase once developmental or damage signals activate the canonical pathway. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:8654923 We show that the full-length CED-3 protein undergoes proteolytic activation to generate a CED-3 cysteine protease and that CED-3 protease activity is required for killing cells by programmed cell death in C. elegans. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Should GO add or revive a caspase autoprocessing term that can distinguish CED-3 self-processing from CED-4-enabled activator activity?
Q: Can the CED-3-dependent manganese dopaminergic-neuron phenotype be resolved as canonical neuron apoptosis, caspase-dependent stress degeneration, or a non-apoptotic CED-3 output?
Q: How should non-apoptotic CED-3 cleavage of GSNL-1 and heterochronic regulators be represented in GO-CAM without implying whole-cell apoptosis?
Experiment: Introduce separation-of-function CED-3 surface mutants in vivo and quantify cleavage of DCR-1, CED-8, GSNL-1, LIN-28 and DISL-2 together with apoptotic cell-corpse counts, presynaptic-cluster elimination and heterochronic reporter timing.
Hypothesis: Distinct substrate-docking surfaces route CED-3 toward apoptotic versus non-apoptotic substrates.
Type: in vivo substrate-cleavage rescue assay
Experiment: Use endogenous fluorescent CED-3 and acute NPP-14 perturbation to follow zymogen localization, CED-4 recruitment, CED-3 processing and caspase-reporter activation in live germ cells after checkpoint induction.
Hypothesis: NPP-14 prevents inappropriate germline apoptosis by tethering and restraining a perinuclear CED-3 zymogen pool until CED-4 accumulates locally.
Type: live-cell imaging and acute depletion
ced-3 encodes a caspase, a cysteine-aspartate protease; CED-3 activity is required for execution of apoptosis and functions in a conserved genetic pathway with CED-4, CED-9, and EGL-1 to regulate apoptosis during C. elegans development.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)