Dark (Drosophila Apaf-1 Related Killer) is a Drosophila homologue of human Apaf-1 and nematode Ced-4 (also known as dapaf-1 and hac-1). Dark exists as two splice forms, the longer containing WD-40 repeats and thus resembling more Apaf-1, whereas the shorter one lacks WD-40 repeats and most closely resembles CED-4. Specific interactions of Dark were detected with the apical caspases Dredd and Dronc. Like Apaf-1, Dark contains an inhibitory WD domain. Dark also associates with cytochrome c. Mutations in Dark suppress normal PCD and ectopic killing by Reaper, Grim and Hid, suggesting that Dark functions downstream of these apoptotic inducers (Rodriguez et al., 1999, Nat. Cell Biol. 1, 272-279).
Dark Cell Death
Slow neuronal death observed, for example, during Huntington's disease. Characterized by strong, cytoplasmic condensation, chromatin clumping, ruffling of the cell membrane, but no blebbing of the nucleus or plasma membrane (Leist and Jaattela, 2001, Nat. Rev. Mol. Cell Biol., 2: 589-98).
dBorg-1 (also known as drob-1, debcl, or dbok) and dBorg-2 (also known as buffy) are the only two clear Bcl-2 family members of Drosophila. Both proteins have BH1, BH2, and BH3 domains and possibly a weak homology BH4 domain. They show the highest overall homology to the mammalian proapoptotic protein Bok/Mtd, and indeed, dBorg-1 and dBorg-2 have pro-apoptotic activity. Genes encoding candidate anti-apoptotic Bcl-2 proteins are not apparent in the Drosophila genome (Brachmann et al., 2000, Curr Biol., 10: 547-550).
DCC is a candidate tumor suppressor gene which is mutated in cases of colonic carcinoma. DCC encodes a receptor for netrin-1, a molecule involved in axon guidance. DCC induces apoptosis in the absence of netrin-1 but blocks apoptosis when bound to netrin-1. DCC is cleaved by Caspase-3 at Asp1290 and this cleavage seems to be required for DCC's apoptotic activity.
Dcp1 is a Drosophila caspase which resembles executioner caspases. Mutations in Dcp1 uncovered a requirement for this gene in somatic and germ-cell development. Other Drosophila caspases are Dronc, Drice, and Dredd (see review by Abrams JM, Trends Cell Biol., 1999, 9: 435-440)
Death Domain: homologous cytoplasmic domain of Death Receptors; by using their DDs, activated death receptors recruit adaptor molecules like FADD, TRADD or DAXX, which eventually mediate the apoptotic signal to the apoptotic machinery. More...
Death receptors are cell surface receptors that transmit apoptosis signals initiated by specific "death ligands". These receptors can activate death caspases within seconds of ligand binding, causing an apoptotic demise of the cell within hours. More
Death Effector Domain: the DED is a specific example of a more global homophilic interaction domain termed CARD, which is found in several caspases with large prodomains. Specific for the DED is, that it is also part of the adaptor protein FADD/MORT 1. DEDD
Death Effector Domain-containing DNA-binding protein (DEDD) was identified by a databank search as a protein containing an N-terminal DED domain. In addition to a DED, it contains two nuclear localization signals and at its C-terminus displays sequence homology with histones. DEDD is highly conserved between homo sapiens and mouse and is ubiquitously expressed. Overexpression of DEDD induces weak apoptosis in 293T cells and results in its translocation into the nucleus where it can bind to DNA and nucleosomes and presumably inhibits transcription. Endogeneous DEDD translocates into the nucleus during CD95-mediated apoptosis, suggesting that DEDD may represent a link between cytoplasmic and nuclear apoptotic events (Stegh et al., 1998, EMBO, 17(29):5974-5986).
Mitochondrial inner transmembrane potential (deltaPsi) More...
Drosophila IAP with apparent anti-apoptotic function.
DNA Fragmentation Factor (45 kDa), human homolog to ICAD (from mouse). It is an inhibitor of a specific endonuclease which cleaves DNA to oligonuceosomal fragments as one of the main features of the apoptotic process. DFF45/ICAD appears to regulate apoptotic DNA fragmentation in collaboration with CIDE proteins. For a review see Nagata, 2000, Exp. Cell Res. 256: 12-18.
Direct IAp Binding protein with LOw pI (Diablo) has been identified as a IAP binding protein and is identical with SMAC (Verhagen et al., 2000, Cell, 102: 43-53).
Drosophila IAPs with BIR domain; both were shown to inhibit cell death. DIAP1 is bound by Reaper, Grim, and Hid and thereby its ability to prevent death-inducing caspase-activity is abolished: this is one possible explanation for the pro-apoptotic activity of Reaper , Grim, and Hid (Goyal et al., 2000, EMBO, 19: 589-597).
Death Inducing Signaling Complex. More...
DNase II is an acid lysosomal DNase possibly involved in a second step of apoptotic DNA degradation besides that mediated by CAD/DFF40 (McIlroy et al., 2000, Genes Dev., 14: 549-558).
DNA-dependent Protein Kinase. DNA-PK is a substrate for caspase-3 and is activated upon DNA damage. One of its substrates is p53. More...
DR5/KILLER is member of the TNFR family of death receptors being activated by its ligand TRAIL. DR5/KILLER was identified to be upregulated in a p53-dependent manner following doxorubicin-treatment.
DED-Recruiting Domain; a domain of modest homology to the DED domain, DRD was found in FLASH, which binds to the DEDs of DADD and caspase-8.
Dream is a Drosophila caspase containing a long prodomain (Vernooy et al., 2000, J. Cell Biol., 150: F69-F74).
Dredd is a Drosophila caspase which resembles initiator caspases, containing a DED-like domain. There appears to be a correlation between Dredd-levels and killing by Reaper and Grim. Reaper, Grim and Hid promote activation of Dredd even in the presence of caspase inhibitors. Dredd RNA was found to accumulate in fly cells specified for cell death. Other Drosophila caspases are Dronc, Dcp1, and Drice (see review by Abrams JM, Trends Cell Biol., 1999, 9: 435-440)
Drice is a Drosophila caspase which resembles executioner caspases. Other Drosophila caspases are Dronc, Dcp1, and Dredd (see review by Abrams JM, Trends Cell Biol., 1999, 9: 435-440)
Dronc is a Drosophila caspase which resembles initiator caspases, containing a CARD domain. Dronc contains an unusual active site (PFCRG instead of QACRG) and is able to cleave behind Asp and Glu residues! Other Drosophila caspases are Dredd, Dcp1, and Drice (see review by Abrams JM, Trends Cell Biol., 1999, 9: 435-440)
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