DEBCL (Drosophila melanogaster)
Description [+]
- Synonyms: DEBCL
- Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
- Short gene description: NA
- Family: Bcl-2 family : multidomain Bcl-2
- Process: cell death (other),
- Pathways:
- Criteria: manually curated
- Curator comment:
- Human ortholog(s): BOK
- WIKI: DEBCL-D_melanogaster
References [+]
- Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery.
- Colussi PA, Quinn LM, Huang DC, Coombe M, Read SH, Richardson H, Kumar S
- Bcl-2 family of proteins are key regulators of apoptosis. Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects. Here, we report the identification and characterization of Debcl, the first Bcl-2 homologue in Drosophila melanogaster. Structurally, Debcl is similar to Bax-like proapoptotic Bcl-2 family members. Ectopic expression of Debcl in cultured cells and in transgenic flies causes apoptosis, which is inhibited by coexpression of the baculovirus caspase inhibitor P35, indicating that Debcl is a proapoptotic protein that functions in a caspase-dependent manner. debcl expression correlates with developmental cell death in specific Drosophila tissues. We also show that debcl genetically interacts with diap1 and dark, and that debcl-mediated apoptosis is not affected by gene dosage of rpr, hid, and grim. Biochemically, Debcl can interact with several mammalian and viral prosurvival Bcl-2 family members, but not with the proapoptotic members, suggesting that it may regulate apoptosis by antagonizing prosurvival Bcl-2 proteins. RNA interference studies indicate that Debcl is required for developmental apoptosis in Drosophila embryos. These results suggest that the main components of the mammalian apoptosis machinery are conserved in insects. J Cell Biol. 2000 Feb 21;148(4):703-14.
- The Bax/Bak ortholog in Drosophila, Debcl, exerts limited control over programmed cell death.
- Galindo KA, Lu WJ, Park JH, Abrams JM
- Bcl-2 family members are pivotal regulators of programmed cell death (PCD). In mammals, pro-apoptotic Bcl-2 family members initiate early apoptotic signals by causing the release of cytochrome c from the mitochondria, a step necessary for the initiation of the caspase cascade. Worms and flies do not show a requirement for cytochrome c during apoptosis, but both model systems express pro- and anti-apoptotic Bcl-2 family members. Drosophila encodes two Bcl-2 family members, Debcl (pro-apoptotic) and Buffy (anti-apoptotic). To understand the role of Debcl in Drosophila apoptosis, we produced authentic null alleles at this locus. Although gross development and lifespans were unaffected, we found that Debcl was required for pruning cells in the developing central nervous system. debcl genetically interacted with the ced-4/Apaf1 counterpart dark, but was not required for killing by RHG (Reaper, Hid, Grim) proteins. We found that debcl(KO) mutants were unaffected for mitochondrial density or volume but, surprisingly, in a model of caspase-independent cell death, heterologous killing by murine Bax required debcl to exert its pro-apoptotic activity. Therefore, although debcl functions as a limited effector of PCD during normal Drosophila development, it can be effectively recruited for killing by mammalian members of the Bcl-2 gene family. Development. 2009 Jan;136(2):275-83. Epub 2008 Dec 15.
- References from Human ortholog(s):
- Nuclear translocation of the pro-apoptotic Bcl-2 family member Bok induces apoptosis.
- Bartholomeusz G, Wu Y, Ali Seyed M, Xia W, Kwong KY, Hortobagyi G, Hung MC
- The anti-apoptotic members of the Bcl-2 family, such as Bcl-2 and Bcl-XL, play a central role in preventing the induction of apoptosis via the intrinsic apoptotic pathway. It has been previously shown that induction of apoptosis by the pro-apoptotic Bcl-2 family member Bok is not antagonized by either Bcl-2 or Bcl-xL, suggesting that Bok might have a unique role in the apoptotic cascade. We showed here that human Bok is the only member of the Bcl-2 family to have a leucine-rich sequence indicative of a nuclear export signal within its BH3 domain. Western blot analysis of nuclear and cytoplasmic fractions identified Bok in both the nucleus and the cytoplasm of HEK 293T cells, HeLa cells, and breast cancer cells, and its nuclear concentration increased after treatment of those cells with leptomycin B, an inhibitor of the exportin Crm1. Immunocytochemistry of flag-tagged Bok confirmed its nuclear localization. Mutating the nuclear export signal of Bok by site-directed mutagenesis resulted in an increase in its nuclear localization and apoptotic activity. We also found that Crm1 interacted with wild-type Bok but not with the mutated form. These results suggest that nuclear export of Bok is a regulated process mediated by Crm1, and constitutes the first report of a link between the apoptotic activity and nuclear localization of a pro-apoptotic member of the Bcl-2 family. Mol Carcinog. 2006 Feb;45(2):73-83.
- Mtd, a novel Bcl-2 family member activates apoptosis in the absence of heterodimerization with Bcl-2 and Bcl-XL.
- Inohara N, Ekhterae D, Garcia I, Carrio R, Merino J, Merry A, Chen S, Nunez G
- We have identified and characterized Mtd, a novel regulator of apoptosis. Sequence analysis revealed that Mtd is a member of the Bcl-2 family of proteins containing conserved BH1, BH2, BH3, and BH4 regions and a carboxyl-terminal hydrophobic domain. In adult tissues, Mtd mRNA was predominantly detected in the brain, liver, and lymphoid tissues, while in the embryo Mtd mRNA was detected in the liver, thymus, lung, and intestinal epithelium. Expression of Mtd promoted the death of primary sensory neurons, 293T cells and HeLa cells, indicating that Mtd is a proapoptotic protein. Unlike all other known death agonists of the Bcl-2 family, Mtd did not bind significantly to the survival-promoting proteins Bcl-2 or Bcl-XL. Furthermore, apoptosis induced by Mtd was not inhibited by Bcl-2 or Bcl-XL. A Mtd mutant with glutamine substitutions of highly conserved amino acids in the BH3 domain retained its ability to promote apoptosis, further indicating that Mtd does not promote apoptosis by heterodimerizing with Bcl-2 or Bcl-XL. Mtd-induced apoptosis was not blocked by broad range synthetic caspase inhibitors z-VAD-fmk or a viral protein CrmA. Mtd is the first example of a naturally occurring Bcl-2 family member that can activate apoptosis independently of heterodimerization with survival-promoting Bcl-2 and Bcl-XL. J Biol Chem. 1998 Apr 10;273(15):8705-10.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Bcl-2 | 146 | 251 |
Protein sequence [+]
debcl | Drosophila melanogaster | 7227 | length:300
MAPTTSPPPKLAKFKSSSLDHEIYTANRRGTIATASSDWKALRGGVGGGAGGPGSVPNPS
NGRSLHAGGPMTRAASTSSLASSTRTMTNYQEYKMDIINQGKCLCGQYIRARLRRAGVLN
RKVTQRLRNILDPGSSHVVYEVFPALNSMGEELERMHPRVYTNISRQLSRAPFGELEDSD
MAPMLLNLVAKDLFRSSITWGKIISIFAVCGGFAIDCVRQGHFDYLQCLIDGLAEIIEDD
LVYWLIDNGGWLGLSRHIRPRVGEFTFLGWLTLFVTISAGAYMVSNVCRRIGGQLYSLLF
NGRSLHAGGPMTRAASTSSLASSTRTMTNYQEYKMDIINQGKCLCGQYIRARLRRAGVLN
RKVTQRLRNILDPGSSHVVYEVFPALNSMGEELERMHPRVYTNISRQLSRAPFGELEDSD
MAPMLLNLVAKDLFRSSITWGKIISIFAVCGGFAIDCVRQGHFDYLQCLIDGLAEIIEDD
LVYWLIDNGGWLGLSRHIRPRVGEFTFLGWLTLFVTISAGAYMVSNVCRRIGGQLYSLLF
Structure links:
- Smartdomain prediction information: SM00337
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL001515-PA | orthology | Aedes |
| Q2PHG8_ANOGA | orthology | Anopheles |
| BOK_CHICK | orthology | Chicken |
| C_intestinalis_ENSCINP00000019812 | orthology | Ciona |
| C_intestinalis_ENSCINP00000016140 | orthology | Ciona |
| NP_001092338.1 | orthology | Cow |
| BOK (1 of 2) | orthology | Fugu |
| BOK (2 of 2) | orthology | Fugu |
| BOK (1 of 2) | orthology | Gasterosteus |
| BOK (2 of 2) | orthology | Gasterosteus |
| BOK | orthology | Gorilla |
| BOK | orthology | Human |
| BOK | orthology | Lyzard |
| BOK | orthology | Macaca |
| BOK (1 of 2) | orthology | Medaka |
| BOK (2 of 2) | orthology | Medaka |
| BOK | orthology | Monodelphis |
| Bok | orthology | Mouse |
| BOK | orthology | Orangutan |
| BOK | orthology | Ornithorhynchus |
| Bok | orthology | Rat |
| BOK (2 of 2) | orthology | Tetraodon |
| BOK (1 of 2) | orthology | Tetraodon |
| BOK | orthology | Zebra finch |
| boka | orthology | Zebrafish |
| bokb | orthology | Zebrafish |
| A_aegypti_AAEL001521-PA | paralogy | Aedes |
| BCL2_CHICK | paralogy | Chicken |
| BCLX_CHICK | paralogy | Chicken |
| BCL2 | paralogy | Chimpanzee |
| BCL2L1 | paralogy | Chimpanzee |
| Q462R3_BOVIN | paralogy | Cow |
| NP_001070954.1 | paralogy | Cow |
| BCL2 | paralogy | Dog |
| NP_001003072.1 | paralogy | Dog |
| Buffy | paralogy | Fly |
| BCL2L1 (1 of 6) | paralogy | Fugu |
| BCL2 | paralogy | Fugu |
| BCL2L1 (2 of 6) | paralogy | Fugu |
| BCL2L1 (1 of 2) | paralogy | Gasterosteus |
| BCL2L1 (2 of 2) | paralogy | Gasterosteus |
| BCL2 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000018978 | paralogy | Gasterosteus |
| BCL2 | paralogy | Gorilla |
| BCL2 | paralogy | Horse |
| BCL2L1 | paralogy | Horse |
| BCL2L1 | paralogy | Human |
| BCL2 | paralogy | Human |
| BCL2L1 | paralogy | Macaca |
| BCL2 | paralogy | Macaca |
| BCL2 | paralogy | Medaka |
| BCL2L1 | paralogy | Medaka |
| BCL2L1 | paralogy | Monodelphis |
| Bcl2l1 | paralogy | Mouse |
| Bcl2 | paralogy | Mouse |
| BCL2 | paralogy | Orangutan |
| BCL2L1 | paralogy | Orangutan |
| Q9MYW4_RABIT | paralogy | Rabbit |
| Bcl2 | paralogy | Rat |
| BCLX_RAT | paralogy | Rat |
| Bcl2a1 | paralogy | Rat |
| BCL2L1 (3 of 3) | paralogy | Tetraodon |
| BCL2L1 (1 of 3) | paralogy | Tetraodon |
| BCL2L1 (2 of 3) | paralogy | Tetraodon |
| BCL2 | paralogy | Tetraodon |
| BCL2L1 | paralogy | Xenopus |
| BCL2L1 | paralogy | Zebra finch |
| BCL2 | paralogy | Zebra finch |
| bcl2l | paralogy | Zebrafish |
| bcl2 | paralogy | Zebrafish |
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Information from other databases [+]
- Gene info from FyBase [?] FBgn0029131
- Ensembl genome browser [?] : FBgn0029131
- Expression info from Arrayexpress [?] : FBgn0029131
- Protein expression from Protein Atlas: [?] FBgn0029131
Click on [?] for more information.
