Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis, a form of cellular suicide, involves the activation of CED-3-related cysteine proteases (caspases). The regulation of caspases by apoptotic signals and the precise mechanism by which they kill the cell remain unknown. In Drosophila, different death-inducing stimuli induce the expression of the apoptotic activator reaper. Cell killing by reaper and two genetically linked apoptotic activators, hid and grim, requires caspase activity. A Drosophila caspase, named Drosophila caspase-1 (DCP-1), was identified and found to be structurally and biochemically similar to Caenorhabditis elegans CED-3. Loss of zygotic DCP-1 function in Drosophila caused larval lethality and melanotic tumors, showing that this gene is essential for normal development.
 ...
PMID:DCP-1, a Drosophila cell death protease essential for development. 899 99

Caspases are involved in the execution of cell death in all multicellular organisms so far studied, including the nematode worm, fruit fly and vertebrates. While Caenorhabditis elegans has only a single identified caspase, CED-3, whose activity is absolutely required for all developmental programmed cell deaths, most mammalian cell types express multiple caspases with varying specificities. The fruit fly Drosophila melanogaster is genetically tractable, less complex than vertebrates and possesses two known caspases, DCP-1 and drICE. The fly may therefore provide a good model system for examining the hierarchy and relative roles of individual caspases in the execution of apoptosis. We have examined the role of drICE in in vitro apoptosis of the D.melanogaster cell line S2. We show that cytoplasmic lysates made from S2 cells undergoing apoptosis induced by either reaper (rpr) expression or cycloheximide treatment contain a caspase activity with DEVD specificity which can cleave p35, lamin DmO, drICE and DCP-1 in vitro, and which can trigger chromatin condensation in isolated nuclei. Using antibodies specific to drICE, we show that immunodepletion of drICE from these lysates is sufficient to remove most measurable in vitro apoptotic activity, and that re-addition of exogenous drICE to such immunodepleted lysates restores apoptotic activity. We conclude that, at least in S2 cells, drICE can be the sole caspase effector of apoptosis.
 ...
PMID:drICE is an essential caspase required for apoptotic activity in Drosophila cells. 932 98

In Drosophila melanogaster, the induction of apoptosis requires three closely linked genes, reaper (rpr), head involution defective (hid), and grim. The products of these genes induce apoptosis by activating a caspase pathway. Two very similar Drosophila caspases, DCP-1 and drICE, have been previously identified. We now show that DCP-1 has a substrate specificity that is remarkably similar to those of human caspase 3 and Caenorhabditis elegans CED-3, suggesting that DCP-1 is a death effector caspase. drICE and DCP-1 have similar yet different enzymatic specificities. Although expression of either in cultured cells induces apoptosis, neither protein was able to induce DNA fragmentation in Drosophila SL2 cells. Ectopic expression of a truncated form of dcp-1 (DeltaN-dcp-1) in the developing Drosophila retina under an eye-specific promoter resulted in a small and rough eye phenotype, whereas expression of the full-length dcp-1 (fl-dcp-1) had little effect. On the other hand, expression of either full-length drICE (fl-drICE) or truncated drICE (DeltaN-drICE) in the retina showed no obvious eye phenotype. 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. Significantly, GMR-rpr and GMR-grim, but not GMR-hid, dramatically enhanced the eye phenotype of GMR-fl-dcp-1 flies. These results indicate that Reaper and Grim, but not HID, can activate DCP-1 in vivo.
 ...
PMID:Biochemical and genetic interactions between Drosophila caspases and the proapoptotic genes rpr, hid, and grim. 1073 94

Many viruses express proteins which prevent the host cell death that their infection would otherwise provoke. Some insect viruses suppress host apoptosis through the expression of caspase inhibitors belonging to the P35 superfamily. Although a number of P35 relatives have been identified, Autographa californica (Ac) P35 and Spodoptera littoralis (Spli) P49 have been the most extensively characterized. AcP35 was found to inhibit caspases via a suicide substrate mechanism: the caspase cleaves AcP35 within its 'reactive site loop' then becomes trapped, irreversibly bound to the cleaved inhibitor. The Maruca vitrata multiple nucleopolyhedrovirus encodes a P35 family member (MaviP35) that exhibits 81% identity to AcP35. We found that this relative shared with AcP35 the ability to inhibit mammalian and insect cell death. Caspase-mediated cleavage within the MaviP35 reactive site loop occurred at a sequence distinct from that in AcP35, and the inhibitory profiles of the two P35 relatives differed. MaviP35 potently inhibited human caspases 2 and 3, DCP-1, DRICE and CED-3 in vitro, but (in contrast to AcP35) only weakly suppressed the proteolytic activity of the initiator human caspases 8, 9 and 10. Although MaviP35 inhibited the AcP35-resistant caspase DRONC in yeast, and was sensitive to cleavage by DRONC in vitro, MaviP35 failed to inhibit the proteolytic activity of bacterially produced DRONC in vitro.
 ...
PMID:Functional and biochemical characterization of the baculovirus caspase inhibitor MaviP35. 2217 98