Dronc is the Drosophila CARD-containing initiator caspase that couples Dark apoptosome assembly to activation of downstream effector caspases such as DrICE and DCP-1. It is synthesized as a zymogen, recruited to Dark through CARD-domain contacts, activated by autocatalytic cleavage and homodimerization, and restrained by DIAP1-dependent binding and ubiquitination until RHG proteins or other death signals relieve that inhibition. Dronc is central to developmental and stress-induced apoptosis and is also reused in restricted nonapoptotic contexts including spermatid individualization, sensory-organ precursor patterning, compensatory proliferation from undead cells, and programmed germ-cell necrosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:10200258 DRONC, an ecdysone-inducible Drosophila caspase. | ACCEPT | Summary: Dronc is a C14 caspase-family cysteine endopeptidase. Reason: Dronc is the catalytic initiator caspase in the Drosophila apoptosome pathway, and biochemical work confirms catalytic activation by autocleavage. Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:10675329 The Drosophila caspase DRONC is regulated by DIAP1. | ACCEPT | Summary: Dronc is a C14 caspase-family cysteine endopeptidase. Reason: Dronc is the catalytic initiator caspase in the Drosophila apoptosome pathway, and biochemical work confirms catalytic activation by autocleavage. Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:15107838 Molecular mechanisms of DrICE inhibition by DIAP1 and remova... | ACCEPT | Summary: Dronc is a C14 caspase-family cysteine endopeptidase. Reason: Dronc is the catalytic initiator caspase in the Drosophila apoptosome pathway, and biochemical work confirms catalytic activation by autocleavage. Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16222340 Drosophila caspase transduces Shaggy/GSK-3beta kinase activi... | ACCEPT | Summary: Dronc is a C14 caspase-family cysteine endopeptidase. Reason: Dronc is the catalytic initiator caspase in the Drosophila apoptosome pathway, and biochemical work confirms catalytic activation by autocleavage. Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16446367 Structure and activation mechanism of the Drosophila initiat... | ACCEPT | Summary: Dronc is a C14 caspase-family cysteine endopeptidase. Reason: Dronc is the catalytic initiator caspase in the Drosophila apoptosome pathway, and biochemical work confirms catalytic activation by autocleavage. Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:21220123 Structure of the Drosophila apoptosome at 6.9 å resolution. | ACCEPT | Summary: Dronc is a C14 caspase-family cysteine endopeptidase. Reason: Dronc is the catalytic initiator caspase in the Drosophila apoptosome pathway, and biochemical work confirms catalytic activation by autocleavage. Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0004197 cysteine-type endopeptidase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Dronc is a C14 caspase-family cysteine endopeptidase. Reason: Dronc is the catalytic initiator caspase in the Drosophila apoptosome pathway, and biochemical work confirms catalytic activation by autocleavage. Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:10984473 An essential role for the caspase dronc in developmentally p... | ACCEPT | Summary: Dronc is a C14 caspase-family cysteine endopeptidase. Reason: Dronc is the catalytic initiator caspase in the Drosophila apoptosome pathway, and biochemical work confirms catalytic activation by autocleavage. Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0004197 cysteine-type endopeptidase activity | ISS PMID:10200258 DRONC, an ecdysone-inducible Drosophila caspase. | ACCEPT | Summary: Dronc is a C14 caspase-family cysteine endopeptidase. Reason: Dronc is the catalytic initiator caspase in the Drosophila apoptosome pathway, and biochemical work confirms catalytic activation by autocleavage. Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0005515 protein binding | IPI PMID:10675329 The Drosophila caspase DRONC is regulated by DIAP1. | MODIFY | Summary: Dronc directly activates cysteine-type endopeptidases (caspases); the row is modified to cysteine-type endopeptidase activator activity, with the apoptotic context carried by the module and core functions. This row's evidence is the Dronc-DrICE interaction, initiator-caspase activation of an effector procaspase. Reason: The replacement is the genus rather than the precomposed GO:0008656 (projects/INVOLVED_IN_PRECOMPOSITION.md); the apoptotic context is carried by the Dark apoptosome step of dmel_rhg_apoptosome_caspase_activation and the core functions. Earlier reasoning, retained for its evidence (its term id updated to the genus): Dronc cleaves DrICE in the Dark apoptosome, so the generic protein-binding import should be replaced by apoptotic cysteine-endopeptidase activator activity. Proposed replacements: cysteine-type endopeptidase activator activity Supporting Evidence: PMID:21220123 Dark-Dronc complex cleaves DrICE |
| GO:0005515 protein binding | IPI PMID:10675329 The Drosophila caspase DRONC is regulated by DIAP1. | REMOVE | Summary: DIAP1 binding is a real inhibitory interaction, but generic protein binding is not an informative Dronc activity. Reason: These IPI rows record DIAP1 inhibitor binding or ubiquitination of Dronc; GO:0005515 does not describe a specific activity of Dronc on DIAP1. |
| GO:0005515 protein binding | IPI PMID:10984473 An essential role for the caspase dronc in developmentally p... | REMOVE | Summary: DIAP1 binding is a real inhibitory interaction, but generic protein binding is not an informative Dronc activity. Reason: These IPI rows record DIAP1 inhibitor binding or ubiquitination of Dronc; GO:0005515 does not describe a specific activity of Dronc on DIAP1. |
| GO:0005515 protein binding | IPI PMID:10984473 An essential role for the caspase dronc in developmentally p... | MODIFY | Summary: The Dronc-Dark interaction is a CARD-mediated apoptosome recruitment interaction, not generic protein binding. Reason: Dronc uses its CARD prodomain to bind Dark during apoptosome assembly; GO:0050700 captures the informative domain-mediated molecular function. Proposed replacements: CARD domain binding Supporting Evidence: PMID:25644603 nearby Dark protomer are indispensable for Dronc activation |
| GO:0005515 protein binding | IPI PMID:12021771 The DIAP1 RING finger mediates ubiquitination of Dronc and i... | REMOVE | Summary: DIAP1 binding is a real inhibitory interaction, but generic protein binding is not an informative Dronc activity. Reason: These IPI rows record DIAP1 inhibitor binding or ubiquitination of Dronc; GO:0005515 does not describe a specific activity of Dronc on DIAP1. |
| GO:0005515 protein binding | IPI PMID:14517550 Molecular mechanism of Reaper-Grim-Hid-mediated suppression ... | REMOVE | Summary: DIAP1 binding is a real inhibitory interaction, but generic protein binding is not an informative Dronc activity. Reason: These IPI rows record DIAP1 inhibitor binding or ubiquitination of Dronc; GO:0005515 does not describe a specific activity of Dronc on DIAP1. |
| GO:0005515 protein binding | IPI PMID:20700104 Metabolic regulation of Drosophila apoptosis through inhibit... | MODIFY | Summary: Dronc directly activates cysteine-type endopeptidases (caspases); the row is modified to cysteine-type endopeptidase activator activity, with the apoptotic context carried by the module and core functions. This row's evidence is the Dronc-DrICE interaction, initiator-caspase activation of an effector procaspase. Reason: The replacement is the genus rather than the precomposed GO:0008656 (projects/INVOLVED_IN_PRECOMPOSITION.md); the apoptotic context is carried by the Dark apoptosome step of dmel_rhg_apoptosome_caspase_activation and the core functions. Earlier reasoning, retained for its evidence (its term id updated to the genus): Dronc cleaves DrICE in the Dark apoptosome, so the generic protein-binding import should be replaced by apoptotic cysteine-endopeptidase activator activity. Proposed replacements: cysteine-type endopeptidase activator activity Supporting Evidence: PMID:21220123 Dark-Dronc complex cleaves DrICE |
| GO:0005515 protein binding | IPI PMID:20700104 Metabolic regulation of Drosophila apoptosis through inhibit... | REMOVE | Summary: DIAP1 binding is a real inhibitory interaction, but generic protein binding is not an informative Dronc activity. Reason: These IPI rows record DIAP1 inhibitor binding or ubiquitination of Dronc; GO:0005515 does not describe a specific activity of Dronc on DIAP1. |
| GO:0005515 protein binding | IPI PMID:20700104 Metabolic regulation of Drosophila apoptosis through inhibit... | MODIFY | Summary: The Dronc-Dark interaction is a CARD-mediated apoptosome recruitment interaction, not generic protein binding. Reason: Dronc uses its CARD prodomain to bind Dark during apoptosome assembly; GO:0050700 captures the informative domain-mediated molecular function. Proposed replacements: CARD domain binding Supporting Evidence: PMID:25644603 nearby Dark protomer are indispensable for Dronc activation |
| GO:0005515 protein binding | IPI PMID:21220123 Structure of the Drosophila apoptosome at 6.9 å resolution. | MODIFY | Summary: The Dronc-Dark interaction is a CARD-mediated apoptosome recruitment interaction, not generic protein binding. Reason: Dronc uses its CARD prodomain to bind Dark during apoptosome assembly; GO:0050700 captures the informative domain-mediated molecular function. Proposed replacements: CARD domain binding Supporting Evidence: PMID:25644603 nearby Dark protomer are indispensable for Dronc activation |
| GO:0005634 nucleus | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | KEEP AS NON CORE | Summary: Dronc is sequestered in Malpighian-tubule nuclei in a specialized developmental context. Reason: The abstract directly reports nuclear sequestration of DRONC and DRICE in Malpighian tubules, a localization context distinct from the core cytoplasmic apoptosome pathway. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic activity is consistent with Dronc function in the Dark apoptosome. Reason: PAINT places a cytoplasm assertion at a Dronc/Casp2-specific node, and direct cellular and apoptosome evidence independently support cytoplasmic Dronc activity. Supporting Evidence: PMID:25644603 nearby Dark protomer are indispensable for Dronc activation |
| GO:0005737 cytoplasm | IDA PMID:10200258 DRONC, an ecdysone-inducible Drosophila caspase. | ACCEPT | Summary: Dronc is predominantly cytoplasmic when expressed in cultured cells. Reason: This localization is consistent with the cytoplasmic Dark apoptosome pathway. Supporting Evidence: PMID:10200258 DRONC was mostly localized in the cytoplasmic fraction of cells |
| GO:0005737 cytoplasm | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | UNDECIDED | Summary: The Malpighian tubule localization paper is abstract-only locally and does not expose the cytoplasm-specific evidence. Reason: The cached abstract foregrounds nuclear sequestration, so defer this IDA cytoplasmic row until the figure-level localization evidence can be checked. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is consistent with the curated UniProt subcellular-location record. Reason: The UniProtKB-SubCell import agrees with direct reports of cytoplasmic Dronc and with the cytoplasmic Dark apoptosome mechanism. Supporting Evidence: PMID:25644603 nearby Dark protomer are indispensable for Dronc activation |
| GO:0005886 plasma membrane | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | UNDECIDED | Summary: The Malpighian tubule localization paper is abstract-only locally and does not verify the plasma-membrane IDA row. Reason: The cached abstract does not mention plasma-membrane Dronc, and the full text is needed before accepting or rejecting this specialized localization. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | MODIFY | Summary: Generic InterPro proteolysis is correct but too broad for this initiator caspase. Reason: Dronc has direct evidence for zymogen autoprocessing during activation; that process is more specific than a caspase-family import to generic proteolysis. Proposed replacements: protein autoprocessing Supporting Evidence: PMID:16446367 The autocleaved Dronc forms a homodimer |
| GO:0006915 apoptotic process | IDA PMID:10984473 An essential role for the caspase dronc in developmentally p... | MODIFY | Summary: Dronc directly promotes apoptotic signaling as the Dark-apoptosome initiator caspase. Reason: The evidence supports a proximal role upstream of effector caspases, so the broad GO:0006915 row should be tightened to positive regulation of apoptotic signaling pathway. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0006915 apoptotic process | IEP PMID:10200258 DRONC, an ecdysone-inducible Drosophila caspase. | MODIFY | Summary: Dronc directly promotes apoptotic signaling as the Dark-apoptosome initiator caspase. Reason: The evidence supports a proximal role upstream of effector caspases, so the broad GO:0006915 row should be tightened to positive regulation of apoptotic signaling pathway. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0006915 apoptotic process | IGI PMID:10675329 The Drosophila caspase DRONC is regulated by DIAP1. | MODIFY | Summary: Dronc directly promotes apoptotic signaling as the Dark-apoptosome initiator caspase. Reason: The evidence supports a proximal role upstream of effector caspases, so the broad GO:0006915 row should be tightened to positive regulation of apoptotic signaling pathway. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0006915 apoptotic process | IGI PMID:12176339 Evolution of TNF signaling mechanisms: JNK-dependent apoptos... | KEEP AS NON CORE | Summary: Dronc is required for Eiger-induced JNK-dependent apoptosis, but this is a context-specific TNF-like branch. Reason: Eiger signaling is an upstream stress/TNF-like input into the Dronc-Dark apoptosome rather than the central Dronc molecular function itself. Supporting Evidence: PMID:12176339 requires the caspase-9 homolog DRONC |
| GO:0006915 apoptotic process | IGI PMID:21844890 NOPO modulates Egr-induced JNK-independent cell death in Dro... | UNDECIDED | Summary: The NOPO/Eiger paper is abstract-only locally and does not expose Dronc-specific evidence. Reason: The abstract supports a NOPO-modulated Eiger caspase branch but does not name Dronc or Dark; defer the IGI row to FlyBase or to full-text verification. |
| GO:0006915 apoptotic process | IGI PMID:31409797 Characterization of TNF-induced cell death in Drosophila rev... | KEEP AS NON CORE | Summary: Eiger-induced apoptosis in the eye is real but is coupled in this study to a distinct necrotic branch. Reason: The paper dissects a context-specific Eiger/JNK system that uses Dronc for both apoptosis and necrosis; keep the row as non-core rather than treating it as the defining Dark-apoptosome pathway. Supporting Evidence: PMID:31409797 apoptosis and necrosis establish a two-layered defense system |
| GO:0006915 apoptotic process | IMP PMID:10200258 DRONC, an ecdysone-inducible Drosophila caspase. | MODIFY | Summary: Dronc directly promotes apoptotic signaling as the Dark-apoptosome initiator caspase. Reason: The evidence supports a proximal role upstream of effector caspases, so the broad GO:0006915 row should be tightened to positive regulation of apoptotic signaling pathway. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0006915 apoptotic process | IMP PMID:10675329 The Drosophila caspase DRONC is regulated by DIAP1. | MODIFY | Summary: Dronc directly promotes apoptotic signaling as the Dark-apoptosome initiator caspase. Reason: The evidence supports a proximal role upstream of effector caspases, so the broad GO:0006915 row should be tightened to positive regulation of apoptotic signaling pathway. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0006915 apoptotic process | IMP PMID:15572131 The apical caspase dronc governs programmed and unprogrammed... | MODIFY | Summary: Dronc directly promotes apoptotic signaling as the Dark-apoptosome initiator caspase. Reason: The evidence supports a proximal role upstream of effector caspases, so the broad GO:0006915 row should be tightened to positive regulation of apoptotic signaling pathway. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0006915 apoptotic process | IMP PMID:15800001 The CARD-carrying caspase Dronc is essential for most, but n... | MODIFY | Summary: Dronc directly promotes apoptotic signaling as the Dark-apoptosome initiator caspase. Reason: The evidence supports a proximal role upstream of effector caspases, so the broad GO:0006915 row should be tightened to positive regulation of apoptotic signaling pathway. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0006915 apoptotic process | IMP PMID:20700104 Metabolic regulation of Drosophila apoptosis through inhibit... | MODIFY | Summary: NADPH/CaMKII regulation modulates Dronc activation in apoptosis. Reason: The direct mechanism is inhibitory phosphorylation of Dronc that gates its activation, so the broad apoptosis row should be tightened to apoptotic signaling regulation. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:20700104 cellular NADPH levels modulate the initiator caspase Dronc through its phosphorylation at S130 |
| GO:0006915 apoptotic process | IPI PMID:10675329 The Drosophila caspase DRONC is regulated by DIAP1. | MODIFY | Summary: Dronc directly promotes apoptotic signaling as the Dark-apoptosome initiator caspase. Reason: The evidence supports a proximal role upstream of effector caspases, so the broad GO:0006915 row should be tightened to positive regulation of apoptotic signaling pathway. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0007291 sperm individualization | IMP PMID:14737191 Multiple apoptotic caspase cascades are required in nonapopt... | KEEP AS NON CORE | Summary: Dronc has a direct, nonapoptotic role in spermatid individualization. Reason: ARK- and HID-dependent local Dronc activation is required at individualization complexes, but the process is explicitly nonapoptotic. Supporting Evidence: PMID:14737191 HID-dependent activation of DRONC occurs at sites of spermatid individualization |
| GO:0007291 sperm individualization | IMP PMID:16362035 The two Drosophila cytochrome C proteins can function in bot... | KEEP AS NON CORE | Summary: The mitochondria/cytochrome-c paper supports a Dronc requirement in spermatid individualization. Reason: This is a direct developmental use of apoptotic caspase machinery for nonlethal cytoplasm removal rather than a core apoptosis row. Supporting Evidence: PMID:16362035 orthologues of the apoptosome components, Ark (Apaf-1) and Dronc (caspase-9), are also required for the proper removal of bulk cytoplasm during spermatogenesis |
| GO:0007417 central nervous system development | IMP PMID:15572131 The apical caspase dronc governs programmed and unprogrammed... | KEEP AS NON CORE | Summary: Dronc mutant animals have supernumerary neurons, but the row captures a developmental outcome. Reason: The direct function is initiator-caspase signaling during cell-number control; central nervous system development is an organismal consequence of losing developmental apoptosis. Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0007516 hemocyte development | IMP PMID:15572131 The apical caspase dronc governs programmed and unprogrammed... | KEEP AS NON CORE | Summary: Dronc mutants have hematopoietic hyperplasia, but hemocyte development is a downstream developmental outcome. Reason: This phenotype reflects failure of Dronc-dependent cell killing during tissue development, not a hemocyte-specific molecular activity. Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0007552 metamorphosis | TAS PMID:11139276 The fly caspases. | KEEP AS NON CORE | Summary: The TAS metamorphosis row is broad but consistent with Dronc acting in ecdysone-regulated tissue histolysis. Reason: The row reflects the metamorphic contexts in which Dronc-dependent programmed cell death occurs rather than a separate core function of the caspase. |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000002 | MODIFY | Summary: The InterPro cysteine-type peptidase import is a correct but less precise parent of caspase activity. Reason: Use the caspase-family cysteine-type endopeptidase term rather than the broader cysteine-type peptidase parent. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:16446367 autocatalytic cleavage of Dronc |
| GO:0008258 head involution | IMP PMID:15572131 The apical caspase dronc governs programmed and unprogrammed... | KEEP AS NON CORE | Summary: Head-involution failure is a developmental phenotype of dronc mutants. Reason: The row is supported genetically but describes an embryonic morphogenetic outcome of defective developmental apoptosis. Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:22555454 Hippo signalling controls Dronc activity to regulate organ s... | MARK AS OVER ANNOTATED | Summary: The Hippo-Dronc organ-size phenotype is too distal for a direct proliferation annotation. Reason: Dronc restrains imaginal-disc overgrowth by executing apoptosis downstream of Hippo-dependent transcriptional control, not by directly regulating the cell cycle or proliferation machinery. |
| GO:0008340 determination of adult lifespan | IMP PMID:16303568 Neuronal expression of p53 dominant-negative proteins in adu... | UNDECIDED | Summary: The adult-lifespan paper is abstract-only locally and does not expose direct Dronc evidence. Reason: The cached abstract/title foreground p53 dominant-negative proteins; without the full text, the Dronc-specific genetic evidence for adult lifespan cannot be checked. |
| GO:0010623 programmed cell death involved in cell development | IMP PMID:16980627 DRONC coordinates cell death and compensatory proliferation. | KEEP AS NON CORE | Summary: Dronc participates in apoptosis-linked compensatory proliferation in imaginal discs. Reason: This is a direct but specialized developmental use of the apoptotic pathway, driven by undead-cell signaling rather than normal Dronc execution alone. Supporting Evidence: PMID:16980627 the Drosophila initiator caspase DRONC governs both apoptosis execution and subsequent compensatory proliferation |
| GO:0012501 programmed cell death | IDA PMID:21120926 Drosophila caspases involved in developmentally regulated pr... | MODIFY | Summary: Dronc contributes to developmentally regulated programmed death of vCrz peptidergic neurons. Reason: The assay is neuron-specific developmental apoptosis; the broad parent programmed cell death should be narrowed to Dronc-positive regulation of apoptotic signaling. Proposed replacements: positive regulation of apoptotic signaling pathway Supporting Evidence: PMID:21120926 was significantly suppressed in dronc-null mutants |
| GO:0016322 neuron remodeling | IGI PMID:23722427 Compartmentalized calcium transients trigger dendrite prunin... | UNDECIDED | Summary: The calcium-transient dendrite-pruning paper is abstract-only locally and does not expose Dronc-specific evidence. Reason: The abstract establishes calcium and calpain requirements but not Dronc, so defer the IGI neuron-remodeling row until full-text figures can be checked. |
| GO:0016322 neuron remodeling | IMP PMID:20445064 Axonal degeneration is regulated by the apoptotic machinery ... | UNDECIDED | Summary: The neurite-pruning paper is abstract-only locally and foregrounds effector caspases rather than Dronc. Reason: Because the cached abstract does not expose Drosophila Dronc-specific evidence, defer this neuron-remodeling row. |
| GO:0016322 neuron remodeling | IMP PMID:23722427 Compartmentalized calcium transients trigger dendrite prunin... | UNDECIDED | Summary: The calcium-transient dendrite-pruning paper is abstract-only locally and does not expose Dronc-specific evidence. Reason: The abstract establishes calcium and calpain requirements but not Dronc, so defer the IMP neuron-remodeling row until full-text figures can be checked. |
| GO:0016540 protein autoprocessing | IDA PMID:16446367 Structure and activation mechanism of the Drosophila initiat... | ACCEPT | Summary: Dronc undergoes autocatalytic processing during activation. Reason: Autoprocessing converts the zymogen into a catalytically stronger dimeric caspase. Supporting Evidence: PMID:16446367 The autocleaved Dronc forms a homodimer |
| GO:0022416 chaeta development | IMP PMID:16222340 Drosophila caspase transduces Shaggy/GSK-3beta kinase activi... | KEEP AS NON CORE | Summary: Dronc-dependent caspase cleavage modulates Shaggy/GSK-3 activity during sensory-organ precursor patterning. Reason: This is a direct, local, nonapoptotic substrate-cleavage role in neural precursor development. Supporting Evidence: PMID:16222340 is cleaved by the Dark-dependent caspase |
| GO:0031638 zymogen activation | IDA PMID:16446367 Structure and activation mechanism of the Drosophila initiat... | ACCEPT | Summary: Dronc zymogen activation by autocleavage is directly supported. Reason: The inactive monomeric zymogen is converted to an active homodimer by autocatalytic cleavage. Supporting Evidence: PMID:16446367 The autocleaved Dronc forms a homodimer |
| GO:0031638 zymogen activation | IMP PMID:16446367 Structure and activation mechanism of the Drosophila initiat... | ACCEPT | Summary: Dronc zymogen activation by autocleavage is genetically supported. Reason: Autocatalytic zymogen activation is the central maturation step for this initiator caspase. Supporting Evidence: PMID:16446367 The autocleaved Dronc forms a homodimer |
| GO:0035006 melanization defense response | IMP PMID:24746817 Necrosis-driven systemic immune response alters SAM metaboli... | UNDECIDED | Summary: The melanization-defense paper is abstract-only locally and the cached abstract does not mention Dronc. Reason: FlyBase may have curated figure-level genetic evidence from the full text, but the local cache only supports a systemic necrosis/immune/metabolism axis. |
| GO:0035070 salivary gland histolysis | IMP PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | UNDECIDED | Summary: The RNAi screen is abstract-only locally and does not expose the salivary-gland histolysis assay. Reason: The abstract supports Dronc as rate-limiting for in vivo apoptosis paradigms but does not verify this exact tissue-specific histolysis term. |
| GO:0035234 ectopic germ cell programmed cell death | IMP PMID:23523076 Alternative germ cell death pathway in Drosophila involves H... | MODIFY | Summary: Dronc acts in an alternative male germ-cell death pathway independent of the canonical apoptosome. Reason: This germ-cell death branch is direct but separable from canonical Dark-apoptosome apoptosis and main executioner caspases. The cited study concerns germ cells eliminated within the testis before meiosis, not errant germ cells outside the gonad or migratory path as required by the definition of ectopic germ cell programmed cell death, so the general programmed cell death term (already present on Dronc) fits; GO has no germ-cell-specific alternative. The same row on HtrA2 is treated identically. Proposed replacements: programmed cell death Supporting Evidence: PMID:23523076 germ cell death (GCD) involves the initiator caspase Dronc |
| GO:0042803 protein homodimerization activity | IDA PMID:16446367 Structure and activation mechanism of the Drosophila initiat... | ACCEPT | Summary: Autocleaved Dronc homodimerizes as part of activation. Reason: The structural activation study showed that cleavage stabilizes Dronc homodimers. Supporting Evidence: PMID:16446367 The autocleaved Dronc forms a homodimer |
| GO:0043293 apoptosome | IDA PMID:21220123 Structure of the Drosophila apoptosome at 6.9 å resolution. | ACCEPT | Summary: Dronc is part of the Dark apoptosome. Reason: Structural reconstitution placed Dronc CARD in the Dark apoptosome and linked those contacts to Dronc activation. Supporting Evidence: PMID:25644603 nearby Dark protomer are indispensable for Dronc activation |
| GO:0043293 apoptosome | IPI PMID:25644603 Structure of the apoptosome: mechanistic insights into activ... | ACCEPT | Summary: Dronc is part of the Dark apoptosome. Reason: The 2015 cryo-EM structure directly resolved the Dark apoptosome bound to Dronc CARD. Supporting Evidence: PMID:25644603 nearby Dark protomer are indispensable for Dronc activation |
| GO:0045476 nurse cell apoptotic process | IGI PMID:17464325 The Drosophila caspases Strica and Dronc function redundantl... | KEEP AS NON CORE | Summary: Dronc redundantly supports nurse-cell programmed death during oogenesis. Reason: The role is a real tissue-specific developmental cell-death function shared with Strica. Supporting Evidence: PMID:17464325 redundancy with dronc, during both mid- and late oogenesis |
| GO:0046667 compound eye retinal cell programmed cell death | IMP PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | UNDECIDED | Summary: The RNAi screen is abstract-only locally and does not expose the retinal-cell apoptosis assay. Reason: The abstract supports Dronc as rate-limiting for in vivo apoptosis paradigms but not the exact compound-eye retinal-cell programmed-death row. |
| GO:0048749 compound eye development | IMP PMID:15572131 The apical caspase dronc governs programmed and unprogrammed... | KEEP AS NON CORE | Summary: Adult structures lacking dronc have fine-patterning defects, including the compound eye. Reason: Compound-eye development is a downstream developmental outcome of Dronc-dependent cell-number control. Supporting Evidence: PMID:15572131 defective for programmed cell death (PCD) |
| GO:0048813 dendrite morphogenesis | IMP PMID:16980964 Local caspase activity directs engulfment of dendrites durin... | UNDECIDED | Summary: The dendrite-pruning paper is abstract-only locally and does not expose Dronc-specific dendrite morphogenesis evidence. Reason: The local abstract establishes local caspase activity in pruning but does not name Dronc, so this row cannot be fully checked. |
| GO:0050700 CARD domain binding | ISM PMID:21220123 Structure of the Drosophila apoptosome at 6.9 å resolution. | ACCEPT | Summary: Dronc binds the Dark apoptosome through CARD-domain interactions. Reason: Structural work shows that Dronc-CARD contacts the Dark CARD and nearby WD40 repeats and that these interactions are required for Dronc activation. Supporting Evidence: PMID:25644603 nearby Dark protomer are indispensable for Dronc activation |
| GO:0097194 execution phase of apoptosis | IDA PMID:15107838 Molecular mechanisms of DrICE inhibition by DIAP1 and remova... | UNDECIDED | Summary: The original DrICE/DIAP1 paper is abstract-only locally and does not expose the Dronc execution-phase assertion. Reason: The cached abstract centers on DIAP1 inhibition of DrICE and does not name Dronc; full-text figure evidence is needed before accepting the exact FlyBase IDA row. |
| GO:0097300 programmed necrotic cell death | IMP PMID:28945745 p53-dependent programmed necrosis controls germ cell homeost... | KEEP AS NON CORE | Summary: Dronc has an atypical nonapoptotic role in programmed germ-cell necrosis. Reason: This p53-dependent germ-cell necrosis branch requires Dronc as a scaffold-like factor independently of catalytic activity, so it is direct but not the core apoptotic caspase function. Supporting Evidence: PMID:28945745 Dronc/Caspase 9 |
| GO:2001235 positive regulation of apoptotic signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT Dronc/Casp2 node supports a conserved positive role in apoptotic signaling. Reason: The IBA is placed at a Dronc plus mouse Casp2 node rather than at the all-caspase root, and Drosophila-specific data support Dronc as an upstream activator of apoptotic caspase signaling. Supporting Evidence: PMID:25644603 nearby Dark protomer are indispensable for Dronc activation |
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Download this section (compressed HTML)Q: Can the catalysis-independent p53/Dronc germ-cell necrosis branch be represented in GO without implying apoptosome assembly or cysteine-endopeptidase activity?
Q: Which Dronc substrates distinguish lethal apoptotic execution from the local nonapoptotic proteolysis used in spermatid individualization, dendrite pruning, and sensory-organ precursor patterning?
Q: How should Eiger/TNF-like signaling to Dronc be modularized in flies, given that JNK input can drive both Dronc-dependent apoptosis and Dronc-dependent necrosis?
Experiment: Introduce endogenous Dronc separation-of-function alleles affecting the CARD, catalytic cysteine, DIAP1-binding motif, and substrate exosites, then measure DrICE cleavage, spermatid individualization, Shaggy cleavage, and spermatogonial necrosis in parallel.
Hypothesis: Distinct Dronc docking surfaces route effector-caspase activation, spermatid individualization, and catalysis-independent germ-cell necrosis.
Type: endogenous structure-function rescue
Experiment: Use purified Dark-Dronc variants and single-particle cryo-EM plus DrICE cleavage kinetics to compare wild-type complexes with CARD-interface mutants identified from the Dronc-CARD/Dark apoptosome structures.
Hypothesis: Dark-Dronc apoptosome geometry determines whether Dronc activates DrICE productively or is held in a restrained zymogen state.
Type: structure-guided reconstitution
Death regulator Nedd2-like caspase (Dronc) encodes an initiator caspase that is essential for caspase-dependent cell death. It is also implicated in the DNA damage response, sperm differentiation and cell specification.
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