Disease relevance of Dcp-1

• Loss of function for the dcp-1 gene, which encodes a caspase, caused female sterility by inhibiting this transfer. dcp-1- nurse cells were defective in the cytoskeletal reorganization and nuclear breakdown that normally accompany this process [1].
• Caspases are implicated in the execution of apoptosis in Drosophila melanogaster by the observation that expression of baculovirus p35, a caspase inhibitor, blocks cell death in vivo in Drosophila [2].
• Recombinant DAMM produced in Escherichia coli shows significant catalytic activity on a pentapeptide caspase substrate [3].
• Independent of caspase activation, Bunyavirus NSs proteins also share with Reaper the ability to directly inhibit cellular protein translation [4].
• These results demonstrate the neuroprotective effect of PTD-XIAP fusion protein against brain injury possibly through the inhibition of caspase [5].

High impact information on Dcp-1

• Drosophila IAP1 (DIAP1) is an endogenous caspase inhibitor that is crucial for regulating cell death during development [6].
• Caspase activation has been extensively studied in the context of apoptosis [6].
• Mutations affecting the Dark protein, an activator of the upstream caspase Dronc, also rescued RacN17 migration defects [7].
• A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration [7].
• Here we show that HID blocks DIAP1's ability to inhibit caspase activity and provide evidence suggesting that RPR and GRIM can act similarly [8].

Biological context of Dcp-1

• Overexpression of the caspase inhibitor DIAP1 suppressed cell death induced by Dcp-1 but had no effect on cell death during late oogenesis [9].
• Because Drice activity was limited in late oogenesis, we examined whether another effector caspase, Dcp-1, could drive the unique morphological events that occur normally in late oogenesis [9].
• The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID [8].
• Our data suggest that DIAP1 instability, mediated through caspase activity and subsequent exposure of the N-end rule pathway, is essential for suppression of apoptosis [10].
• Although active DCP-1 protein cleaves full-length DCP-1 and full-length drICE in vitro, GMR-DeltaN-dcp-1 did not enhance the eye phenotype of GMR-fl-dcp-1 or GMR-fl-drICE flies [11].

Anatomical context of Dcp-1

• The Drosophila caspase Ice is important for many apoptotic cell deaths and for spermatid individualization, a nonapoptotic process [12].
• This limited caspase activation in dying nurse cells may prevent destruction of the nurse cell cytoskeleton and the connected oocyte [9].
• Lack of involvement of mitochondrial factors in caspase activation in a Drosophila cell-free system [13].
• Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning [14].
• These observations establish a role for the mitochondria in caspase activation during spermatogenesis [15].

Associations of Dcp-1 with chemical compounds

• Depletion of the DIAP1 protein in Drosophila S2 cells or the Sf-IAP protein in Spodoptera frugiperda Sf21 cells by RNA interference (RNAi) or cycloheximide treatment resulted in rapid and widespread caspase-dependent apoptosis [16].
• Both Ac-YVAD aldehyde and Ac-DEVD aldehyde, specific inhibitors of caspase 1- and caspase 3-like proteases, respectively, inhibited the FasC-induced death of Drosophila cells [17].
• Ceramide generation and caspase activation occurred nearly simultaneously, each detectable at 2-2.5 h and maximal at 6 h [18].
• In most cases, apoptotic cell death culminates in the activation of the caspase family of cysteine proteases, leading to the orderly dismantling and elimination of the cell [19].
• Here we show that the Drosophila caspase DRONC cleaves COOH-terminal to glutamate as well as aspartate [20].

Physical interactions of Dcp-1

• Ecdysone receptor directly binds the promoter of the Drosophila caspase dronc, regulating its expression in specific tissues [21].

Enzymatic interactions of Dcp-1

• We found that DIAP1 is cleaved by a caspase early after the initiation of apoptosis [22].

Regulatory relationships of Dcp-1

• Because loss of DIAP1 is sufficient to promote caspase activation, these mechanisms should promote apoptosis [23].
• Conversely, we demonstrate that overexpression of Dnr1 blocks apoptotic caspase activity and prevents induction of apoptosis in tissue culture assays [24].
• Skl interacts with Drosophila and mammalian IAPs and can promote caspase activation in the presence of IAPs [25].
• In contrast to previous reports, we show that the dronc eye ablation phenotype can be suppressed by coexpression of the baculoviral caspase inhibitor p35 [26].
• The Drosophila nuclear factor-kappaB (NF-kappaB)-like transcription factor Relish is activated by an endoproteolytic cleavage step mediated by the Drosophila caspase Dredd [27].

Other interactions of Dcp-1

• Two very similar Drosophila caspases, DCP-1 and drICE, have been previously identified [11].
• Here, we report the isolation of a mutant allele of the Drosophila effector caspase drICE as a strong suppressor of hid- (head involution defective-) induced apoptosis [28].
• Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator [29].
• This suggests that L or Ser loss-of-function triggers both caspase-dependent and -independent cell death [30].
• We demonstrate that these processes are regulated by dp53 in a manner that is independent of DNA-damage sensing but that requires the initiator caspase Dronc [31].

Analytical, diagnostic and therapeutic context of Dcp-1

• The role of cytochrome c (Cyt c) in caspase activation has largely been established from mammalian cell-culture studies, but much remains to be learned about its physiological relevance in situ [32].
• Sequence analysis revealed that human CLARP contains two amino-terminal death effector domains fused to a carboxyl-terminal caspase-like domain [33].
• Immunoprecipitation analysis showed that both CED-4 and CED-4 (K165R) bind directly to Drosophila caspase drICE, and the overexpression of CED-4 (K165R) inhibits CED-4-, ecdysone-, or cycloheximide-dependent caspase activation in S2 cells [34].

References