DrICE is the major Drosophila short-prodomain effector caspase activated downstream of the Dark/Dronc apoptosome. It is a C14 cysteine endopeptidase that cleaves apoptotic substrates during the execution phase of apoptosis, is restrained by DIAP1 and DIAP2 BIR-domain IAP contacts, and is also reused in limited nonlethal outputs including spermatid individualization, nurse-cell removal, sensory-organ precursor patterning, and innate-immune damping through DIF or Diap2 cleavage and binding.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004197 cysteine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT C14-caspase node correctly propagates cysteine endopeptidase activity to DrICE. Reason: The PANTHER node spans experimentally characterized metazoan executioner caspases, and DrICE has direct biochemical and genetic evidence for cysteine-type endopeptidase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000047947 SUPPORTS TRANSFER The all-caspase node transfers the conserved catalytic C14 endopeptidase activity, which DrICE retains. Supporting Evidence: PMID:9184225 cleaves baculovirus p35 and Drosophila lamin DmO PMID:16887831 important non-redundant role |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:15107838 Molecular mechanisms of DrICE inhibition by DIAP1 and remova... | ACCEPT | Summary: DrICE is an effector C14 cysteine endopeptidase. Reason: DrICE is the major Drosophila short-prodomain effector caspase: it cleaves apoptotic substrates and nonapoptotic substrates after activation by the Dark/Dronc pathway. Supporting Evidence: PMID:9184225 cleaves baculovirus p35 and Drosophila lamin DmO PMID:16887831 important non-redundant role |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16222340 Drosophila caspase transduces Shaggy/GSK-3beta kinase activi... | ACCEPT | Summary: DrICE is an effector C14 cysteine endopeptidase. Reason: DrICE is the major Drosophila short-prodomain effector caspase: it cleaves apoptotic substrates and nonapoptotic substrates after activation by the Dark/Dronc pathway. Supporting Evidence: PMID:16222340 cleaved by the Dark-dependent caspase |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | ACCEPT | Summary: DrICE is an effector C14 cysteine endopeptidase. Reason: DrICE is the major Drosophila short-prodomain effector caspase: it cleaves apoptotic substrates and nonapoptotic substrates after activation by the Dark/Dronc pathway. Supporting Evidence: PMID:18166655 drICE activity |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:23940367 Caspase-dependent regulation of the ubiquitin-proteasome sys... | ACCEPT | Summary: DrICE is an effector C14 cysteine endopeptidase. Reason: DrICE is the major Drosophila short-prodomain effector caspase: it cleaves apoptotic substrates and nonapoptotic substrates after activation by the Dark/Dronc pathway. Supporting Evidence: PMID:23940367 active caspases can simultaneously cleave Grim at Asp132 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:36002459 Apoptotic caspase inhibits innate immune signaling by cleavi... | ACCEPT | Summary: DrICE is an effector C14 cysteine endopeptidase. Reason: DrICE is the major Drosophila short-prodomain effector caspase: it cleaves apoptotic substrates and nonapoptotic substrates after activation by the Dark/Dronc pathway. Supporting Evidence: PMID:36002459 degradation of DIF |
| GO:0004197 cysteine-type endopeptidase activity | IEA GO_REF:0000002 | ACCEPT | Summary: DrICE is an effector C14 cysteine endopeptidase. Reason: DrICE is the major Drosophila short-prodomain effector caspase: it cleaves apoptotic substrates and nonapoptotic substrates after activation by the Dark/Dronc pathway. Supporting Evidence: PMID:9184225 cleaves baculovirus p35 and Drosophila lamin DmO PMID:16887831 important non-redundant role |
| GO:0004197 cysteine-type endopeptidase activity | ISS PMID:9184225 Identification of a Drosophila melanogaster ICE/CED-3-relate... | ACCEPT | Summary: Early ISS rows to human effector caspases correctly infer the conserved DrICE catalytic activity. Reason: The ISS donors are human executioner caspases and the DrICE cloning paper directly confirmed cysteine-protease cleavage of p35 and lamin DmO, so the inferred activity is sound. Supporting Evidence: PMID:9184225 cleaves baculovirus p35 and Drosophila lamin DmO |
| GO:0004197 cysteine-type endopeptidase activity | ISS PMID:9184225 Identification of a Drosophila melanogaster ICE/CED-3-relate... | ACCEPT | Summary: Early ISS rows to human effector caspases correctly infer the conserved DrICE catalytic activity. Reason: The ISS donors are human executioner caspases and the DrICE cloning paper directly confirmed cysteine-protease cleavage of p35 and lamin DmO, so the inferred activity is sound. Supporting Evidence: PMID:9184225 cleaves baculovirus p35 and Drosophila lamin DmO |
| GO:0005515 protein binding | IPI PMID:10675329 The Drosophila caspase DRONC is regulated by DIAP1. | REMOVE | Summary: The Dronc-DrICE interaction records DrICE as an effector-caspase substrate, not a specific DrICE binding activity. Reason: Dronc binds, cleaves, and activates DrICE. The Dronc-side annotation was narrowed to apoptotic cysteine-endopeptidase activator activity; the reciprocal generic protein-binding row on substrate DrICE adds no molecular function performed by DrICE. Supporting Evidence: PMID:21220123 Dark-Dronc complex cleaves DrICE |
| GO:0005515 protein binding | IPI PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | MODIFY | Summary: DIAP1 binding is an inhibitory BIR-domain interaction rather than generic protein binding. Reason: DIAP1 inhibits DrICE through a BIR1 groove, so the useful assertion is BIR domain binding. Proposed replacements: BIR domain binding Supporting Evidence: PMID:15107838 inhibition of the effector caspase DrICE PMID:15107838 through its BIR1 domain |
| GO:0005515 protein binding | IPI PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | MODIFY | Summary: DIAP2 binding is a mechanism-based IAP interaction rather than generic protein binding. Reason: DIAP2 binds active DrICE, forms a mechanism-based inhibitory complex, and ubiquitylates DrICE; BIR domain binding is the informative molecular-function term for this IAP contact. Proposed replacements: BIR domain binding Supporting Evidence: PMID:18166655 DIAP2 robustly ubiquitylates drICE in vivo PMID:34262145 forming a complex with Diap2 |
| GO:0005515 protein binding | IPI PMID:20700104 Metabolic regulation of Drosophila apoptosis through inhibit... | REMOVE | Summary: The cached metabolic-regulation paper uses DrICE as the Dronc substrate and does not establish a DrICE-side binding activity. Reason: The accessible full text shows Dronc-mediated cleavage of DrICE downstream of metabolic control of Dronc. That is enzyme-substrate cleavage by Dronc, not an informative generic binding function of DrICE. Supporting Evidence: PMID:20700104 Dronc-mediated cleavage of drICE |
| GO:0005634 nucleus | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | KEEP AS NON CORE | Summary: DrICE can be sequestered in nuclei of Malpighian tubules during metamorphosis. Reason: The abstract reports nuclear sequestration of DRICE and DRONC in Malpighian tubules and lack of enzymatic processing there. This is a true tissue-specific localization rather than the core site of apoptotic effector-caspase action. Supporting Evidence: PMID:21035895 sequestered in the nucleus |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm is the canonical site of DrICE activation and effector-caspase activity. Reason: The inherited cytoplasmic location fits soluble DrICE activation downstream of Dark/Dronc and direct S2-cell evidence for cytoplasmic apoptotic processing. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000047947 SUPPORTS TRANSFER The PAINT node transfers the broad cytoplasmic active site of metazoan caspases; DrICE is no exception. Supporting Evidence: PMID:9184225 Induction of apoptosis by rpr overexpression |
| GO:0005737 cytoplasm | IDA PMID:14668412 Caspases function in autophagic programmed cell death in Dro... | ACCEPT | Summary: Cytoplasmic localization is consistent with DrICE effector-caspase activation in dying larval salivary glands. Reason: Although the cached abstract does not expose the figure-level DrICE staining behind this FlyBase IDA row, cytoplasmic localization agrees with the accepted inherited active compartment for a soluble effector caspase downstream of Dark/Dronc. Supporting Evidence: PMID:14668412 caspases are not only used during apoptosis |
| GO:0005737 cytoplasm | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | ACCEPT | Summary: Cytoplasmic DrICE in Malpighian tubules is a specialized localization context compatible with the core cytoplasmic DrICE claim. Reason: FlyBase curated this IDA row from a localization study of apoptotic proteins in Malpighian tubules, and the cytoplasm assertion is compatible with the accepted cytoplasmic active site of DrICE even though the cached abstract emphasizes nuclear sequestration of unprocessed DRICE. Supporting Evidence: PMID:21035895 sequestered in the nucleus |
| GO:0005886 plasma membrane | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | UNDECIDED | Summary: The plasma-membrane DrICE row is not verifiable from the cached abstract. Reason: The local abstract discusses DRICE sequestration and differential processing in Malpighian tubules but does not expose plasma-membrane localization evidence. Supporting Evidence: PMID:21035895 differential activity of apoptotic proteins in Malpighian tubules |
| GO:0006508 proteolysis | IDA PMID:23940367 Caspase-dependent regulation of the ubiquitin-proteasome sys... | KEEP AS NON CORE | Summary: DrICE proteolysis is true but less informative than its effector-caspase activity and execution-phase role. Reason: As a caspase, DrICE directly cleaves protein substrates. GO:0006508 is a broad parent, so keep it as non-core while using cysteine-type endopeptidase activity and execution phase of apoptosis for the core function. Supporting Evidence: PMID:23940367 active caspases can simultaneously cleave Grim at Asp132 |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: DrICE proteolysis is true but less informative than its effector-caspase activity and execution-phase role. Reason: As a caspase, DrICE directly cleaves protein substrates. GO:0006508 is a broad parent, so keep it as non-core while using cysteine-type endopeptidase activity and execution phase of apoptosis for the core function. Supporting Evidence: PMID:23940367 active caspases can simultaneously cleave Grim at Asp132 |
| GO:0006915 apoptotic process | IBA GO_REF:0000033 | MODIFY | Summary: DrICE executes apoptosis, so the broad apoptotic-process row should be tightened to execution phase. Reason: The row is biologically sound but imprecise: DrICE sits downstream of Dronc and DCP-1 as an effector caspase that dismantles cells during the execution phase. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000047947 SUPPORTS SOURCE BUT NOT TARGET The PAINT node supports inherited effector-caspase apoptosis biology, but the propagated top-level term is a broad ancestor of the execution-phase term already supported for DrICE. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:16980627 the effector caspase DRICE as crucial executioners of apoptosis PMID:16887831 important non-redundant role |
| GO:0006915 apoptotic process | IGI PMID:31409797 Characterization of TNF-induced cell death in Drosophila rev... | MODIFY | Summary: DrICE executes apoptosis, so the broad apoptotic-process row should be tightened to execution phase. Reason: The row is biologically sound but imprecise: DrICE sits downstream of Dronc and DCP-1 as an effector caspase that dismantles cells during the execution phase. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:16980627 the effector caspase DRICE as crucial executioners of apoptosis PMID:16887831 important non-redundant role |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000002 | MODIFY | Summary: The InterPro C14-peptidase row is correct but can be narrowed to cysteine-type endopeptidase activity. Reason: DrICE is not merely a generic cysteine peptidase; direct biochemical work establishes C14 cysteine-type endopeptidase activity. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:9184225 cleaves baculovirus p35 and Drosophila lamin DmO |
| GO:0010165 response to X-ray | IMP PMID:16887831 The Drosophila caspase Ice is important for many apoptotic c... | KEEP AS NON CORE | Summary: X-ray response is a stress context in which DrICE-dependent apoptosis is induced. Reason: Ice-null cells resist X-irradiation-induced death, supporting a real but stimulus-specific effector-caspase role. Supporting Evidence: PMID:16887831 markedly resistant to several stresses, including X-irradiation |
| GO:0010623 programmed cell death involved in cell development | IMP PMID:16980627 DRONC coordinates cell death and compensatory proliferation. | MODIFY | Summary: The programmed-cell-death parent is true but less precise than DrICE execution-phase apoptosis. Reason: The evidence places DrICE at the downstream effector-caspase step of apoptotic PCD rather than at an unspecified programmed-cell-death process. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:16980627 the effector caspase DRICE as crucial executioners of apoptosis PMID:16887831 important non-redundant role |
| GO:0012501 programmed cell death | IDA PMID:21120926 Drosophila caspases involved in developmentally regulated pr... | MODIFY | Summary: The programmed-cell-death parent is true but less precise than DrICE execution-phase apoptosis. Reason: The evidence places DrICE at the downstream effector-caspase step of apoptotic PCD rather than at an unspecified programmed-cell-death process. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:21120926 vCrz PCD requires both ice and dcp-1 functions |
| GO:0012501 programmed cell death | IMP PMID:16887831 The Drosophila caspase Ice is important for many apoptotic c... | MODIFY | Summary: The programmed-cell-death parent is true but less precise than DrICE execution-phase apoptosis. Reason: The evidence places DrICE at the downstream effector-caspase step of apoptotic PCD rather than at an unspecified programmed-cell-death process. Proposed replacements: execution phase of apoptosis Supporting Evidence: PMID:16980627 the effector caspase DRICE as crucial executioners of apoptosis PMID:16887831 important non-redundant role |
| GO:0016322 neuron remodeling | IEA GO_REF:0000117 | UNDECIDED | Summary: The neurite-pruning evidence is abstract-only locally and does not expose DrICE-specific data. Reason: The abstract supports fly effector caspases acting in neurite pruning in parallel with Wld(S), but the cached evidence does not name DrICE or distinguish it from Dcp-1. Supporting Evidence: PMID:20445064 parallel to the fly effector caspases |
| GO:0016322 neuron remodeling | IMP PMID:20445064 Axonal degeneration is regulated by the apoptotic machinery ... | UNDECIDED | Summary: The neurite-pruning evidence is abstract-only locally and does not expose DrICE-specific data. Reason: The abstract supports fly effector caspases acting in neurite pruning in parallel with Wld(S), but the cached evidence does not name DrICE or distinguish it from Dcp-1. Supporting Evidence: PMID:20445064 parallel to the fly effector caspases |
| GO:0031625 ubiquitin protein ligase binding | IDA PMID:34262145 Drice restrains Diap2-mediated inflammatory signalling and i... | KEEP AS NON CORE | Summary: DrICE binds the Diap2 ubiquitin ligase in a nonapoptotic intestinal immune-brake complex. Reason: DrICE forms a complex with the IAP E3 ligase Diap2 that drives proteasomal degradation of the DrICE-Diap2 complex and restrains basal intestinal NF-kappaB signaling. This binding is direct but peripheral to DrICE apoptotic execution. Supporting Evidence: PMID:18166655 DIAP2 robustly ubiquitylates drICE in vivo PMID:34262145 forming a complex with Diap2 |
| GO:0035070 salivary gland histolysis | IMP PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | UNDECIDED | Summary: The RNAi-screen salivary-gland row is abstract-only locally and not DrICE-specific. Reason: The abstract identifies DrICE as rate-limiting in several apoptosis paradigms but does not expose the exact salivary-gland histolysis assay behind this row. Supporting Evidence: PMID:16485033 Dronc, drICE, Strica and Decay are rate limiting for apoptosis |
| GO:0043525 positive regulation of neuron apoptotic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: The PAINT neuronal-apoptosis term is over-specific for DrICE. Reason: DrICE executes apoptotic death in many tissues. PAINT propagation from vertebrate and worm neuronal apoptosis donors to positive regulation of neuron apoptotic process overstates a cell-type-specific regulatory role for the fly effector caspase. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH Sources checked: PANTHER:PTN000047947 SUPPORTS SOURCE BUT NOT TARGET The node supports conserved caspase apoptosis, but not a neuron-specific positive-regulation term on the general fly effector caspase. Supporting Evidence: PMID:16980627 the effector caspase DRICE as crucial executioners of apoptosis PMID:16887831 important non-redundant role |
| GO:0045476 nurse cell apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: DrICE and Dcp-1 act redundantly in late nurse-cell death during oogenesis. Reason: Late nurse-cell death is a direct tissue-specific use of DrICE/Dcp-1 effector caspases, but it is not the core generic execution-phase assertion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00043473 SUPPORTS TRANSFER The rule propagates a true, tissue-specific nurse-cell apoptosis function for DrICE. Supporting Evidence: PMID:17464325 resulting in persisting nurse cell |
| GO:0045476 nurse cell apoptotic process | IGI PMID:17464325 The Drosophila caspases Strica and Dronc function redundantl... | KEEP AS NON CORE | Summary: DrICE and Dcp-1 act redundantly in late nurse-cell death during oogenesis. Reason: Late nurse-cell death is a direct tissue-specific use of DrICE/Dcp-1 effector caspases, but it is not the core generic execution-phase assertion. Supporting Evidence: PMID:17464325 resulting in persisting nurse cell |
| GO:0045751 negative regulation of Toll signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: DrICE directly attenuates Toll signaling by cleaving the NF-kappaB factor DIF. Reason: Purified fly effector caspases cleave DIF and suppress Toll/NF-kappaB output. This is a direct immune-signaling role, but it is separate from core apoptotic execution. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00084359 SUPPORTS TRANSFER The ARBA assertion matches a directly assayed nonapoptotic DrICE/DCP-1 brake on Toll signaling. Supporting Evidence: PMID:36002459 degradation of DIF |
| GO:0045751 negative regulation of Toll signaling pathway | IMP PMID:36002459 Apoptotic caspase inhibits innate immune signaling by cleavi... | KEEP AS NON CORE | Summary: DrICE directly attenuates Toll signaling by cleaving the NF-kappaB factor DIF. Reason: Purified fly effector caspases cleave DIF and suppress Toll/NF-kappaB output. This is a direct immune-signaling role, but it is separate from core apoptotic execution. Supporting Evidence: PMID:36002459 degradation of DIF |
| 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 retinal-cell row is abstract-only locally and not exactly verifiable. Reason: The abstract supports DrICE as rate-limiting in different in vivo apoptosis paradigms but does not expose the compound-eye retinal-cell PCD assay behind the row. Supporting Evidence: PMID:16485033 Dronc, drICE, Strica and Decay are rate limiting for apoptosis |
| GO:0048515 spermatid differentiation | IMP PMID:16887831 The Drosophila caspase Ice is important for many apoptotic c... | KEEP AS NON CORE | Summary: DrICE participates in spermatid differentiation through a nonlethal caspase pathway. Reason: Ice-null analysis supports a direct but partly redundant requirement in spermatid differentiation, a nonapoptotic process already seen for the Dark/Dronc module. Supporting Evidence: PMID:16887831 non-apoptotic process of spermatid differentiation |
| GO:0061060 negative regulation of peptidoglycan recognition protein signaling pathway | IMP PMID:34262145 Drice restrains Diap2-mediated inflammatory signalling and i... | KEEP AS NON CORE | Summary: DrICE restrains basal PGRP/Imd signaling in the intestinal epithelium through Diap2. Reason: Commensal bacteria create basal PGRP-LCx input, while active DrICE binds Diap2 and targets the complex for degradation, thereby limiting Imd/NF-kappaB target activation. Supporting Evidence: PMID:34262145 Drice, by restraining Diap2 |
| GO:0097194 execution phase of apoptosis | IDA PMID:15107838 Molecular mechanisms of DrICE inhibition by DIAP1 and remova... | ACCEPT | Summary: Execution phase of apoptosis is the precise core biological process for DrICE. Reason: DrICE is a downstream effector caspase activated by Dronc and inhibited by DIAP1 until RHG proteins relieve that inhibition, placing it in execution rather than upstream apoptotic signaling. Supporting Evidence: PMID:15107838 inhibition of the effector caspase DrICE PMID:15107838 through its BIR1 domain |
| GO:0097194 execution phase of apoptosis | IEA GO_REF:0000117 | ACCEPT | Summary: Execution phase of apoptosis is the precise core biological process for DrICE. Reason: DrICE is a downstream effector caspase activated by Dronc and inhibited by DIAP1 until RHG proteins relieve that inhibition, placing it in execution rather than upstream apoptotic signaling. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00090101 SUPPORTS TRANSFER The ARBA model correctly maps the fly effector caspase to apoptotic execution. Supporting Evidence: PMID:15107838 inhibition of the effector caspase DrICE PMID:15107838 through its BIR1 domain |
| GO:1990525 BIR domain binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: DrICE binds IAP BIR domains during regulation by DIAP1 and DIAP2. Reason: BIR-domain binding captures direct IAP inhibitory contacts, but those contacts regulate the effector caspase rather than define its catalytic execution role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00090447 SUPPORTS TRANSFER The ARBA BIR-domain-binding assertion is supported by DIAP1/DIAP2 contacts with DrICE. Supporting Evidence: PMID:15107838 inhibition of the effector caspase DrICE PMID:15107838 through its BIR1 domain PMID:18166655 DIAP2 robustly ubiquitylates drICE in vivo PMID:34262145 forming a complex with Diap2 |
| GO:1990525 BIR domain binding | IPI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | KEEP AS NON CORE | Summary: DrICE binds Diap2, a BIR-domain IAP. Reason: The source abstract specifically reports active DrICE binding by DIAP2, and later work shows DrICE/Diap2 complex formation during intestinal immune restraint. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE PMID:34262145 forming a complex with Diap2 |
| GO:1990525 BIR domain binding | IPI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | KEEP AS NON CORE | Summary: DrICE binds the DIAP1 BIR1 domain. Reason: Although the cached RNAi-screen abstract does not expose the DIAP1 binding assay, independent structural work directly demonstrates DIAP1 BIR1 inhibition of DrICE; keep the BIR-domain molecular function as a real regulatory interaction. Supporting Evidence: PMID:15107838 inhibition of the effector caspase DrICE PMID:15107838 through its BIR1 domain |
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Download this section (compressed HTML)Q: Which substrate-specific cleavage events distinguish lethal DrICE/Dcp-1 apoptotic execution from low-level nonapoptotic DrICE activity in spermatids, SOP cells, nurse cells, and the intestinal epithelium?
Q: How are DrICE-DIAP1 and DrICE-DIAP2 BIR-domain interactions rewired between apoptotic inhibition, Diap2-dependent intestinal immune restraint, and pathogen-induced Imd signaling?
Q: Does DrICE have a direct role in axon or dendrite pruning in vivo, or are the abstract-only neuron-remodeling rows mostly evidence for the effector-caspase branch as a whole?
Experiment: Use endogenous Drice alleles with active-site-proximal substrate-recognition substitutions and Diap2-binding-interface substitutions, then compare apoptotic substrate cleavage, Drosocin/Diptericin induction, Diap2 stability, and survival after commensal and pathogenic bacterial challenges.
Hypothesis: DrICE execution of apoptosis and DrICE restraint of commensal-triggered Imd signaling require separable substrate contacts.
Type: structure-guided endogenous separation-of-function genetics
Experiment: Profile cleaved substrates by quantitative N-terminomics in matched wild-type, Drice-null, Dcp-1-null, and double-mutant apoptotic tissues, including eye discs, nurse cells, vCrz neurons, and spermatids.
Hypothesis: Dcp-1 buffers DrICE only in selected developmental death programs rather than throughout apoptotic execution.
Type: comparative degradomics
Death related ICE-like caspase (Drice) encodes a major effector apoptotic caspase. It is essential for both developmental and damaged induced cell death, as well as several non-apoptotic vital cellular processes. It is activated by the product of Dark and the initiator caspase encoded by Dronc and is inhibited by the inhibitor of apoptosis encoded by Diap1.
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