Gene Symbol: Dark
Description: Death-associated APAF1-related killer
Alias: APAF-1, APAF1, ARK, Apaf, Apaf-1, Apaf1, Ark, CG6829, D-Apaf-1, DARK, Dapaf-1, Dapaf-1/HAC-1, Dark/Apaf-I, Dark/Dapaf-1/HAC1, Dark/Hac-1/dApaf-1, Dark/Hac-1/dApaf1, Dmel\CG6829, Hac-1, Hac-1/Dark, Hac1, anon-53Fa, apaf-1, apaf1, arc, ark, dAPAF-1, dApaf-1, dApaf-1/DARK/HAC-1, dApaf1, dArk, dapaf, dapaf-1, dapaf-1L, dapaf-1S, dark, dark/dapaf-1/hac-1, dark/hac-1/dapaf-1, hac-1, hac1, l(2)SH0173, Death-associated APAF1-related killer, Apaf-1 related, Apaf-1 related killer, Apaf-1-related killer, Apaf-1-related-killer, CG6829-PA, CG6829-PB, Dark-PA, Dark-PB, apaf1-related killer, dark, drosophila Apaf-1-related killer, lethal (2) SH0173, transcription unit 1
Species: fruit fly

Top Publications

  1. Quinn L, Dorstyn L, Mills K, Colussi P, Chen P, Coombe M, et al. An essential role for the caspase dronc in developmentally programmed cell death in Drosophila. J Biol Chem. 2000;275:40416-24 pubmed
    ..Dronc also interacts, both genetically and biochemically, with the CED-4/Apaf-1 fly homolog, Dark...
  2. Dorstyn L, Read S, Cakouros D, Huh J, Hay B, Kumar S. The role of cytochrome c in caspase activation in Drosophila melanogaster cells. J Cell Biol. 2002;156:1089-98 pubmed
    The release of cytochrome c from mitochondria is necessary for the formation of the Apaf-1 apoptosome and subsequent activation of caspase-9 in mammalian cells...
  3. Kanuka H, Kuranaga E, Takemoto K, Hiratou T, Okano H, Miura M. Drosophila caspase transduces Shaggy/GSK-3beta kinase activity in neural precursor development. EMBO J. 2005;24:3793-806 pubmed
    ..isoform encoded by the sgg gene and essential for the negative regulation of Wingless signaling, is cleaved by the Dark-dependent caspase...
  4. Kornbluth S, White K. Apoptosis in Drosophila: neither fish nor fowl (nor man, nor worm). J Cell Sci. 2005;118:1779-87 pubmed
    ..Thus, although Drosophila, worms and humans share a host of apoptotic regulators, the way in which they function may not be identical. ..
  5. Choi Y, Lee G, Park J. Programmed cell death mechanisms of identifiable peptidergic neurons in Drosophila melanogaster. Development. 2006;133:2223-32 pubmed
    ..Significant delay of vCrz-cell death was observed in mutants that lack dronc or dark functions, indicating that formation of an apoptosome is necessary, but not sufficient, for timely execution of the ..
  6. Mendes C, Arama E, Brown S, Scherr H, Srivastava M, Bergmann A, et al. Cytochrome c-d regulates developmental apoptosis in the Drosophila retina. EMBO Rep. 2006;7:933-9 pubmed
    ..is no apoptosis in mutant retinal tissues for the Drosophila homologues of apoptotic protease-activating factor 1 (Ark) and caspase 9 (Dronc)...
  7. Yin V, Thummel C, Bashirullah A. Down-regulation of inhibitor of apoptosis levels provides competence for steroid-triggered cell death. J Cell Biol. 2007;178:85-92 pubmed
    ..It also provides a molecular mechanism for the acquisition of competence in steroid signaling pathways. ..
  8. Ditzel M, Wilson R, Tenev T, Zachariou A, Paul A, Deas E, et al. Degradation of DIAP1 by the N-end rule pathway is essential for regulating apoptosis. Nat Cell Biol. 2003;5:467-73 pubmed
    ..We suggest that DIAP1 safeguards cell viability through the coordinated mutual destruction of itself and associated active caspases. ..
  9. Kumar S, Doumanis J. The fly caspases. Cell Death Differ. 2000;7:1039-44 pubmed
    ..The presence of multiple caspases in Drosophila indicates that apoptotic pathways in insects are likely to be as complex as in vertebrates. ..

More Information


  1. Yuan S, Yu X, Topf M, Dorstyn L, Kumar S, Ludtke S, et al. Structure of the Drosophila apoptosome at 6.9 å resolution. Structure. 2011;19:128-40 pubmed publisher
    The Drosophila Apaf-1 related killer forms an apoptosome in the intrinsic cell death pathway. In this study we show that Dark forms a single ring when initiator procaspases are bound...
  2. Lee C, Simon C, Woodard C, Baehrecke E. Genetic mechanism for the stage- and tissue-specific regulation of steroid triggered programmed cell death in Drosophila. Dev Biol. 2002;252:138-48 pubmed
    ..and E93 loss-of-function mutants indicate that these genes regulate stage-specific transcription of the rpr, hid, ark, dronc, and crq cell death genes...
  3. Colussi P, Quinn L, Huang D, Coombe M, Read S, Richardson H, et al. Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery. J Cell Biol. 2000;148:703-14 pubmed
    ..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...
  4. Steller H. Drosophila p53: meeting the Grim Reaper. Nat Cell Biol. 2000;2:E100-2 pubmed
    ..The recent discovery of a Drosophila orthologue of the p53 tumour suppressor promises new insights into the complex function, regulation and evolution of one of the most intensely studied human disease proteins. ..
  5. Akdemir F, Farkas R, Chen P, Juhasz G, Medved ová L, Sass M, et al. Autophagy occurs upstream or parallel to the apoptosome during histolytic cell death. Development. 2006;133:1457-65 pubmed
    ..Using in vivo and ex vivo assays, we demonstrate a global apoptogenic requirement for dark, the fly ortholog of Apaf1, and show that a required focus of dark(-) organismal lethality maps to the central nervous system...
  6. Danial N, Korsmeyer S. Cell death: critical control points. Cell. 2004;116:205-19 pubmed
    ..The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics. ..
  7. Zhou L, Steller H. Distinct pathways mediate UV-induced apoptosis in Drosophila embryos. Dev Cell. 2003;4:599-605 pubmed
    ..in pregastrulation embryos, both UVB and UVC promote apoptosis via transcriptional induction of the Drosophila Apaf-1/ced-4 homolog...
  8. Muro I, Hay B, Clem R. The Drosophila DIAP1 protein is required to prevent accumulation of a continuously generated, processed form of the apical caspase DRONC. J Biol Chem. 2002;277:49644-50 pubmed
    ..Co-silencing of dronc or dark largely suppressed this apoptosis, indicating that DIAP1 is normally required to inhibit an activity dependent on ..
  9. Muro I, Monser K, Clem R. Mechanism of Dronc activation in Drosophila cells. J Cell Sci. 2004;117:5035-41 pubmed
    ..Suppression of the oligomerizing factor Dark by RNA interference revealed that Dark is required for Dronc autoprocessing at E352, whereas RNA interference of ..
  10. Zimmermann K, Ricci J, Droin N, Green D. The role of ARK in stress-induced apoptosis in Drosophila cells. J Cell Biol. 2002;156:1077-87 pubmed
    ..Although a homologue for CED-4/apoptotic protease-activating factor (Apaf)-1 has been described in Drosophila, its exact function and the role of the mitochondrial pathway in its activation ..
  11. Hu S, Yang X. dFADD, a novel death domain-containing adapter protein for the Drosophila caspase DREDD. J Biol Chem. 2000;275:30761-4 pubmed
    ..Procaspase activation is mediated by death adapter proteins such as the mammalian proteins FADD and Apaf-1 and the Caenorhabditis elegans protein CED-4...
  12. Suissa Y, Ziv O, Dinur T, Arama E, Gerlitz O. The NAB-Brk signal bifurcates at JNK to independently induce apoptosis and compensatory proliferation. J Biol Chem. 2011;286:15556-64 pubmed publisher
    ..pro-apoptotic proteins Reaper and Hid, which in turn promote activation of caspases by the apoptosome components Ark and Dronc. The other signal induces CP in a manner that is independent of the death signal, Dronc, or Dp53...
  13. Zhou L, Song Z, Tittel J, Steller H. HAC-1, a Drosophila homolog of APAF-1 and CED-4 functions in developmental and radiation-induced apoptosis. Mol Cell. 1999;4:745-55 pubmed
    We have identified a Drosophila homolog of Apaf-1 and ced-4, termed hac-1. Like mammalian APAF-1, HAC-1 can activate caspases in a dATP-dependent manner in vitro...
  14. Chew S, Akdemir F, Chen P, Lu W, Mills K, Daish T, et al. The apical caspase dronc governs programmed and unprogrammed cell death in Drosophila. Dev Cell. 2004;7:897-907 pubmed
    ..dronc genetically interacts with the Ced4/Apaf1 counterpart, Dark, and adult structures lacking dronc are disrupted for fine patterning...
  15. Cakouros D, Daish T, Mills K, Kumar S. An arginine-histone methyltransferase, CARMER, coordinates ecdysone-mediated apoptosis in Drosophila cells. J Biol Chem. 2004;279:18467-71 pubmed
    ..Thus, the chromatin-modifying protein, CARMER, modulates cell death by controlling the hormone-dependent expression of the core cell death machinery. ..
  16. Bergmann A, Yang A, Srivastava M. Regulators of IAP function: coming to grips with the grim reaper. Curr Opin Cell Biol. 2003;15:717-24 pubmed
    ..The apoptosis-inducing genes grim, reaper and hid modulate these mechanisms, and determine the outcome. ..
  17. Lee C, Cooksey B, Baehrecke E. Steroid regulation of midgut cell death during Drosophila development. Dev Biol. 2002;250:101-11 pubmed
    ..Dying midguts express the rpr, hid, ark, dronc, and crq cell death genes, suggesting that the core cell death machinery is involved in larval midgut cell ..
  18. Wang L, Lam G, Thummel C. Med24 and Mdh2 are required for Drosophila larval salivary gland cell death. Dev Dyn. 2010;239:954-64 pubmed publisher
    ..This study identifies novel mechanisms for controlling the destruction of larval tissues during Drosophila metamorphosis and provides new directions for our understanding of steroid-triggered programmed cell death. ..
  19. Baehrecke E. Steroid regulation of programmed cell death during Drosophila development. Cell Death Differ. 2000;7:1057-62 pubmed
    ..This article reviews the current knowledge of steroid signaling and the regulation of programmed cell death during development of Drosophila. ..
  20. Moon N, Frolov M, Kwon E, Di Stefano L, Dimova D, Morris E, et al. Drosophila E2F1 has context-specific pro- and antiapoptotic properties during development. Dev Cell. 2005;9:463-75 pubmed
    ..These loss-of-function experiments demonstrate that E2F cannot be classified simply as a pro- or antiapoptotic factor. Instead, the overall role of E2F in the damage response varies greatly and depends on the cellular context. ..
  21. Kanuka H, Sawamoto K, Inohara N, Matsuno K, Okano H, Miura M. Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator. Mol Cell. 1999;4:757-69 pubmed
    We identified a Drosophila Apaf-1/CED-4 homolog gene, dapaf-1. Alternative splicing results in two dapaf-1 mRNA species, which encode distinct forms of caspase activator, Dapaf-1L (Apaf-1 type) and Dapaf-1S (CED-4 type)...
  22. Arama E, Agapite J, Steller H. Caspase activity and a specific cytochrome C are required for sperm differentiation in Drosophila. Dev Cell. 2003;4:687-97 pubmed
    ..These observations suggest that an apoptosis-like mechanism is required for spermatid differentiation in Drosophila. ..
  23. Leulier F, Ribeiro P, Palmer E, Tenev T, Takahashi K, Robertson D, et al. Systematic in vivo RNAi analysis of putative components of the Drosophila cell death machinery. Cell Death Differ. 2006;13:1663-74 pubmed
    ..While Hid killing requires Strica, Decay, Dronc/Dark and drICE, apoptosis triggered by DIAP1 depletion merely relied upon Dronc/Dark and drICE...
  24. Mills K, Daish T, Harvey K, Pfleger C, Hariharan I, Kumar S. The Drosophila melanogaster Apaf-1 homologue ARK is required for most, but not all, programmed cell death. J Cell Biol. 2006;172:809-15 pubmed
    The Apaf-1 protein is essential for cytochrome c-mediated caspase-9 activation in the intrinsic mammalian pathway of apoptosis...
  25. Rodriguez A, Chen P, Oliver H, Abrams J. Unrestrained caspase-dependent cell death caused by loss of Diap1 function requires the Drosophila Apaf-1 homolog, Dark. EMBO J. 2002;21:2189-97 pubmed
    In mammals and Drosophila, apoptotic caspases are under positive control via the CED-4/Apaf-1/Dark adaptors and negative control via IAPs (inhibitor of apoptosis proteins)...
  26. Yu X, Wang L, Acehan D, Wang X, Akey C. Three-dimensional structure of a double apoptosome formed by the Drosophila Apaf-1 related killer. J Mol Biol. 2006;355:577-89 pubmed
    The Drosophila Apaf-1 related killer (Dark) forms an apoptosome that activates Dronc, an apical procaspase in the intrinsic cell death pathway. To study this process, we assembled a large Dark complex in the presence of dATP...
  27. Srivastava M, Scherr H, Lackey M, Xu D, Chen Z, Lu J, et al. ARK, the Apaf-1 related killer in Drosophila, requires diverse domains for its apoptotic activity. Cell Death Differ. 2007;14:92-102 pubmed
    In mammals and Drosophila, apoptotic caspases are under positive control of the CED-4-like proteins Apaf-1 and ARK, respectively. In an EMS-mutagenesis screen, we isolated 33 ark mutants as recessive suppressors of hid-induced apoptosis...
  28. Winbush A, Weeks J. Steroid-triggered, cell-autonomous death of a Drosophila motoneuron during metamorphosis. Neural Dev. 2011;6:15 pubmed publisher
    ..the function of EcR-B isoforms, the death-activating gene, reaper (but not hid), and the apoptosome component, Dark. PCD was blocked by expression of the caspase inhibitor p35 but unaffected by manipulating Diap1...
  29. Abrams J. An emerging blueprint for apoptosis in Drosophila. Trends Cell Biol. 1999;9:435-40 pubmed
    ..The death inducers Reaper, Grim and Hid relay signals, possibly through IAPs (inhibitor of apoptosis proteins) and Dark (an Apaf-1/Ced-4 homologue), to trigger caspase function...
  30. Lee C, Wendel D, Reid P, Lam G, Thummel C, Baehrecke E. E93 directs steroid-triggered programmed cell death in Drosophila. Mol Cell. 2000;6:433-43 pubmed
    ..Furthermore, expression of E93 is sufficient to induce programmed cell death. We propose that the steroid induction of E93 determines a programmed cell death response during development. ..
  31. Shapiro P, Hsu H, Jung H, Robbins E, Ryoo H. Regulation of the Drosophila apoptosome through feedback inhibition. Nat Cell Biol. 2008;10:1440-6 pubmed publisher
    ..Specifically, the adaptor protein Apaf-1 lowers the level of its associated initiator caspase Dronc, without triggering apoptosis...
  32. Rodriguez A, Oliver H, Zou H, Chen P, Wang X, Abrams J. Dark is a Drosophila homologue of Apaf-1/CED-4 and functions in an evolutionarily conserved death pathway. Nat Cell Biol. 1999;1:272-9 pubmed
    Here we identify a new gene, dark, which encodes a Drosophila homologue of mammalian Apaf-1 and Caenorhabditis elegans CED-4, cell-death proteins...
  33. Herz H, Chen Z, Scherr H, Lackey M, Bolduc C, Bergmann A. vps25 mosaics display non-autonomous cell survival and overgrowth, and autonomous apoptosis. Development. 2006;133:1871-80 pubmed
    ..In summary, the phenotypic analysis of vps25 mutants highlights the importance of receptor downregulation by endosomal protein sorting for appropriate tissue homeostasis, and may serve as a model for human cancer. ..
  34. Xu D, Woodfield S, Lee T, Fan Y, Antonio C, Bergmann A. Genetic control of programmed cell death (apoptosis) in Drosophila. Fly (Austin). 2009;3:78-90 pubmed
    ..Here, we review the key players of the cell death pathway in Drosophila and discuss their roles in apoptotic and non-apoptotic processes. ..
  35. Denton D, Shravage B, Simin R, Mills K, Berry D, Baehrecke E, et al. Autophagy, not apoptosis, is essential for midgut cell death in Drosophila. Curr Biol. 2009;19:1741-6 pubmed publisher
    ..The initiator caspase Dronc and its activator Ark are required for the death of salivary glands, but not for midgut removal [2, 3]...
  36. Arama E, Bader M, Srivastava M, Bergmann A, Steller H. The two Drosophila cytochrome C proteins can function in both respiration and caspase activation. EMBO J. 2006;25:232-43 pubmed
    ..Furthermore, orthologues of the apoptosome components, Ark (Apaf-1) and Dronc (caspase-9), are also required for the proper removal of bulk cytoplasm during spermatogenesis...
  37. Muro I, Means J, Clem R. Cleavage of the apoptosis inhibitor DIAP1 by the apical caspase DRONC in both normal and apoptotic Drosophila cells. J Biol Chem. 2005;280:18683-8 pubmed
    ..These results expand our knowledge of the events that occur in the Drosophila apoptosome prior to and after receiving an apoptotic signal. ..
  38. Martin S. Destabilizing influences in apoptosis: sowing the seeds of IAP destruction. Cell. 2002;109:793-6 pubmed
    ..Recent developments suggest that ubiquitin-proteasome mediated destruction of the Drosophila IAP, DIAP1, is a key event during the initiation of programmed cell death in the fly. ..
  39. Igaki T, Yamamoto Goto Y, Tokushige N, Kanda H, Miura M. Down-regulation of DIAP1 triggers a novel Drosophila cell death pathway mediated by Dark and DRONC. J Biol Chem. 2002;277:23103-6 pubmed
    ..suppressed by a reduction in the Drosophila caspase DRONC or the Drosophila apoptotic protease-activating factor-1 (Apaf-1) homolog, Dark...
  40. Peterson C, Carney G, Taylor B, White K. reaper is required for neuroblast apoptosis during Drosophila development. Development. 2002;129:1467-76 pubmed
    ..Although both the ecdysone hormone receptor complex and p53 directly regulate rpr transcription, rpr was found to play a limited role in inducing apoptosis in response to either of these signals. ..
  41. Muro I, Berry D, Huh J, Chen C, Huang H, Yoo S, et al. The Drosophila caspase Ice is important for many apoptotic cell deaths and for spermatid individualization, a nonapoptotic process. Development. 2006;133:3305-15 pubmed
    ..Finally, we demonstrate that Ice participates in, but is not absolutely required for, the non-apoptotic process of spermatid differentiation. ..
  42. Williams D, Kondo S, Krzyzanowska A, Hiromi Y, Truman J. Local caspase activity directs engulfment of dendrites during pruning. Nat Neurosci. 2006;9:1234-6 pubmed
    ..A new genetically encoded caspase probe revealed that caspase activity is confined to the degenerating dendrites of pruning neurons. ..
  43. Lee C, Baehrecke E. Steroid regulation of autophagic programmed cell death during development. Development. 2001;128:1443-55 pubmed
    ..In contrast, E93 expression is sufficient to induce the removal of cells by phagocytes in the absence of the H99 genes. These studies indicate that apoptosis and autophagy utilize some common regulatory mechanisms. ..
  44. Dorstyn L, Kumar S. A biochemical analysis of the activation of the Drosophila caspase DRONC. Cell Death Differ. 2008;15:461-70 pubmed
    ..caspase DRONC, is tightly inhibited by DIAP1 and removal of DIAP1 permits activation of DRONC by the Drosophila Apaf-1-related killer, ARK. ARK is proposed to facilitate DRONC oligomerisation and autoprocessing at residue E352...
  45. Huh J, Vernooy S, Yu H, Yan N, Shi Y, Guo M, et al. Multiple apoptotic caspase cascades are required in nonapoptotic roles for Drosophila spermatid individualization. PLoS Biol. 2004;2:E15 pubmed
    ..many viable cells through interactions with ARK, the Drosophila homolog of the mammalian death-activating adaptor APAF-1. This leads to unrestrained activity of DRONC and other DIAP1-inhibitable caspases activated by DRONC...
  46. Fan Y, Bergmann A. The cleaved-Caspase-3 antibody is a marker of Caspase-9-like DRONC activity in Drosophila. Cell Death Differ. 2010;17:534-9 pubmed publisher
    ..In contrast, mutants of the apoptosome components DRONC (Caspase-9-like) and ARK (Apaf-1 related) do not label with the cleaved-Caspase-3 antibody...
  47. Dorstyn L, Mills K, Lazebnik Y, Kumar S. The two cytochrome c species, DC3 and DC4, are not required for caspase activation and apoptosis in Drosophila cells. J Cell Biol. 2004;167:405-10 pubmed
    In Drosophila, activation of the apical caspase DRONC requires the apoptotic protease-activating factor homologue, DARK. However, unlike caspase activation in mammals, DRONC activation is not accompanied by the release of cytochrome c ..
  48. Fan Y, Lee T, Xu D, Chen Z, Lamblin A, Steller H, et al. Dual roles of Drosophila p53 in cell death and cell differentiation. Cell Death Differ. 2010;17:912-21 pubmed publisher
    ..These findings provide new insights into the pathways activated by Dp53 and reveal that Dp53 incorporates functions of multiple p53 family members. ..
  49. Arya R, White K. Cell death in development: Signaling pathways and core mechanisms. Semin Cell Dev Biol. 2015;39:12-9 pubmed publisher
    ..Understanding how the cell death is regulated during development may provide insight into how this process can be manipulated in the treatment of disease. ..
  50. Obata F, Kuranaga E, Tomioka K, Ming M, Takeishi A, Chen C, et al. Necrosis-driven systemic immune response alters SAM metabolism through the FOXO-GNMT axis. Cell Rep. 2014;7:821-33 pubmed publisher
    ..We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis. ..
  51. Griciuc A, Roux M, Merl J, Giangrande A, Hauck S, Aron L, et al. Proteomic survey reveals altered energetic patterns and metabolic failure prior to retinal degeneration. J Neurosci. 2014;34:2797-812 pubmed publisher
    ..Genetic inactivation of the endoplasmic reticulum stress-induced JNK/TRAF1 axis as well as the APAF-1/caspase-9 axis, activated by damaged mitochondria, dramatically suppressed Rh1(P37H)-induced PN degeneration, ..
  52. Khammari A, Agnes F, Gandille P, Pret A. Physiological apoptosis of polar cells during Drosophila oogenesis is mediated by Hid-dependent regulation of Diap1. Cell Death Differ. 2011;18:793-805 pubmed publisher
    ..Hid is specifically necessary for PC apoptosis, as well as the initiator caspase Dronc and its adaptor Dark/Apaf-1, and likely several effector caspases, in particular Drice...
  53. Xu P, Guo M, Hay B. MicroRNAs and the regulation of cell death. Trends Genet. 2004;20:617-24 pubmed
  54. Meier P, Finch A, Evan G. Apoptosis in development. Nature. 2000;407:796-801 pubmed
    ..Dysfunctions in the regulation or execution of cell suicide are implicated in a wide range of developmental abnormalities and diseases. ..
  55. White K. The third horseman takes wing. Nat Cell Biol. 1999;1:E123-4 pubmed
  56. Verghese S, Bedi S, Kango Singh M. Hippo signalling controls Dronc activity to regulate organ size in Drosophila. Cell Death Differ. 2012;19:1664-76 pubmed publisher
    ..The Hippo-Dronc connection has implications in control of overall organ size and other growth regulatory mechanisms like compensatory proliferation and cell competition. ..
  57. Oshima K, Takeda M, Kuranaga E, Ueda R, Aigaki T, Miura M, et al. IKK epsilon regulates F actin assembly and interacts with Drosophila IAP1 in cellular morphogenesis. Curr Biol. 2006;16:1531-7 pubmed
    ..This IKK epsilon function involves the negative regulation of the nonapoptotic activity of DIAP1. ..
  58. Shklyar B, Levy Adam F, Mishnaevski K, Kurant E. Caspase activity is required for engulfment of apoptotic cells. Mol Cell Biol. 2013;33:3191-201 pubmed publisher
  59. Sevrioukov E, Burr J, Huang E, Assi H, Monserrate J, Purves D, et al. Drosophila Bcl-2 proteins participate in stress-induced apoptosis, but are not required for normal development. Genesis. 2007;45:184-93 pubmed
    ..Our results demonstrate that developmental PCD regulation in the fly does not rely upon the Bcl-2 proteins, but that they provide an added layer of protection in the apoptotic response to stress. ..