Gene Symbol: skl
Description: sickle
Alias: BcDNA:RE14076, CG13701, Dmel\CG13701, Skl, meph, veto, sickle, CG13701-PA, mephisto, skl-PA
Species: fruit fly

Top Publications

  1. Truscott M, Islam A, Lopez Bigas N, Frolov M. mir-11 limits the proapoptotic function of its host gene, dE2f1. Genes Dev. 2011;25:1820-34 pubmed publisher
    ..Thus, our data support a model in which the coexpression of miR-11 limits the proapoptotic function of its host gene, dE2f1, upon DNA damage by directly modulating a dE2F1-dependent apoptotic transcriptional program. ..
  2. Tan Y, Yamada Mabuchi M, Arya R, St Pierre S, Tang W, Tosa M, et al. Coordinated expression of cell death genes regulates neuroblast apoptosis. Development. 2011;138:2197-206 pubmed publisher
    ..during embryogenesis requires the coordinated expression of the cell death genes grim and reaper, and possibly sickle. These genes are clustered in a 140 kb region of the third chromosome and show overlapping patterns of expression...
  3. Choi Y, Lee G, Park J. Programmed cell death mechanisms of identifiable peptidergic neurons in Drosophila melanogaster. Development. 2006;133:2223-32 pubmed
  4. Wing J, Karres J, Ogdahl J, Zhou L, Schwartz L, Nambu J. Drosophila sickle is a novel grim-reaper cell death activator. Curr Biol. 2002;12:131-5 pubmed
    ..In this report, we describe a novel grim-reaper gene, termed sickle, that resides adjacent to reaper...
  5. Miguel Aliaga I, Thor S, Gould A. Postmitotic specification of Drosophila insulinergic neurons from pioneer neurons. PLoS Biol. 2008;6:e58 pubmed publisher
    ..These studies reveal striking similarities between the transcription factors regulating insulin expression in insect neurons and mammalian pancreatic beta-cells. ..
  6. Vazquez Pianzola P, Hernandez G, Suter B, Rivera Pomar R. Different modes of translation for hid, grim and sickle mRNAs in Drosophila. Cell Death Differ. 2007;14:286-95 pubmed
    ..In contrast, sickle mRNA is translated in a cap-dependent manner in all these assays...
  7. Leaman D, Chen P, Fak J, Yalcin A, Pearce M, Unnerstall U, et al. Antisense-mediated depletion reveals essential and specific functions of microRNAs in Drosophila development. Cell. 2005;121:1097-108 pubmed
    ..this is achieved by differential posttranscriptional repression of the proapoptotic factors hid, grim, reaper, and sickle. Our findings demonstrate that microRNAs act as specific and essential regulators in a wide range of developmental ..
  8. 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. ..
  9. Brennecke J, Stark A, Russell R, Cohen S. Principles of microRNA-target recognition. PLoS Biol. 2005;3:e85 pubmed

More Information


  1. Srinivasula S, Datta P, Kobayashi M, Wu J, Fujioka M, Hegde R, et al. sickle, a novel Drosophila death gene in the reaper/hid/grim region, encodes an IAP-inhibitory protein. Curr Biol. 2002;12:125-30 pubmed
    ..Here we describe the functional characterization of the novel Drosophila cell death protein Sickle (Skl), which binds to IAPs and neutralizes their apoptotic inhibitory activity...
  2. Christich A, Kauppila S, Chen P, Sogame N, Ho S, Abrams J. The damage-responsive Drosophila gene sickle encodes a novel IAP binding protein similar to but distinct from reaper, grim, and hid. Curr Biol. 2002;12:137-40 pubmed
    ..Here we describe a fourth member of this genetic group, sickle (skl), which maps just outside of the H99 deletion...
  3. Bartel D. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281-97 pubmed
    ..Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes. ..
  4. Claveria C, Torres M. Mitochondrial apoptotic pathways induced by Drosophila programmed cell death regulators. Biochem Biophys Res Commun. 2003;304:531-7 pubmed
    ..Recent molecular and cellular analyses suggest, however, that the mechanisms of action of the main programmed cell death regulators in Drosophila include a canonical mitochondrial pathway. ..
  5. Merino M, Rhiner C, López Gay J, Buechel D, Hauert B, Moreno E. Elimination of unfit cells maintains tissue health and prolongs lifespan. Cell. 2015;160:461-76 pubmed publisher
    ..On the contrary, improving the efficiency of cell selection is beneficial for tissue health and extends lifespan. ..
  6. Juhasz G, Sass M. Hid can induce, but is not required for autophagy in polyploid larval Drosophila tissues. Eur J Cell Biol. 2005;84:491-502 pubmed
    ..Our results show that the large, post-mitotic larval cells do not react or activate autophagy in response to the same strong apoptotic stimuli that trigger apoptosis in small, mitotically active imaginal disc cells. ..
  7. McCann C, Holohan E, Das S, Dervan A, Larkin A, Lee J, et al. The Ataxin-2 protein is required for microRNA function and synapse-specific long-term olfactory habituation. Proc Natl Acad Sci U S A. 2011;108:E655-62 pubmed publisher
  8. Blanch M, Piñeyro D, Bernués J. New insights for Drosophila GAGA factor in larvae. R Soc Open Sci. 2015;2:150011 pubmed publisher
    ..GAGA factor activity thus correlates with the global changes in gene expression that take place at the embryo-to-larva and, later, at the larva-to-pupa transitions. ..
  9. Ge W, Chen Y, Weng R, Lim S, Buescher M, Zhang R, et al. Overlapping functions of microRNAs in control of apoptosis during Drosophila embryogenesis. Cell Death Differ. 2012;19:839-46 pubmed publisher
    ..functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective (hid), grim and sickle (skl)...
  10. Brachmann C, Cagan R. Patterning the fly eye: the role of apoptosis. Trends Genet. 2003;19:91-6 pubmed
    ..But, we have yet to understand how this signaling is regulated spatially to result in such precision. In this article, we describe and speculate on the role of selective cell death during maturation of the fly eye. ..
  11. Link N, Kurtz P, O Neal M, García Hughes G, Abrams J. A p53 enhancer region regulates target genes through chromatin conformations in cis and in trans. Genes Dev. 2013;27:2433-8 pubmed publisher
    ..Therefore, a defined p53 enhancer region is sufficient for long-range chromatin interactions that enable multigenic regulation. ..
  12. Holcik M. Drosophila veto puts a stop to cell survival. Trends Cell Biol. 2002;12:213 pubmed
  13. Sato K, Hayashi Y, Ninomiya Y, Shigenobu S, Arita K, Mukai M, et al. Maternal Nanos represses hid/skl-dependent apoptosis to maintain the germ line in Drosophila embryos. Proc Natl Acad Sci U S A. 2007;104:7455-60 pubmed
    ..In addition, we demonstrate that hid acts in concert with another RHG gene, sickle (skl), to induce apoptosis...
  14. Denton D, Kumar S. Studying Apoptosis in Drosophila. Cold Spring Harb Protoc. 2015;2015:609-13 pubmed publisher
    ..The focus of this discussion is to introduce methodologies for monitoring apoptosis during Drosophila development and also in Drosophila cell lines. ..
  15. Jassim O, Fink J, Cagan R. Dmp53 protects the Drosophila retina during a developmentally regulated DNA damage response. EMBO J. 2003;22:5622-32 pubmed
    ..These in vivo results demonstrate that the cellular effects of DNA damage depend on the developmental status of the tissue. ..
  16. Baena Lopez L, Alexandre C, Mitchell A, Pasakarnis L, Vincent J. Accelerated homologous recombination and subsequent genome modification in Drosophila. Development. 2013;140:4818-25 pubmed publisher
    ..Therefore, our method retains the advantages of homologous recombination while capitalising on the mutagenic power of CRISPR...
  17. Yan N, Wu J, Chai J, Li W, Shi Y. Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim. Nat Struct Mol Biol. 2004;11:420-8 pubmed
    ..These studies define novel molecular mechanisms for the inhibition and activation of a representative D. melanogaster effector caspase. ..
  18. Mohseni N, McMillan S, Chaudhary R, Mok J, Reed B. Autophagy promotes caspase-dependent cell death during Drosophila development. Autophagy. 2009;5:329-38 pubmed
    ..Conversely, upregulation of autophagy results in caspase-dependent premature AS dissociation. These observations are consistent with the interpretation that autophagy is a prerequisite for caspase-dependent cell death in the AS. ..
  19. Elenbaas J, Mouawad R, Henry R, Arnosti D, Payankaulam S. Role of Drosophila retinoblastoma protein instability element in cell growth and proliferation. Cell Cycle. 2015;14:589-97 pubmed publisher
    ..Intriguingly, cancer associated mutations affecting RB homologs p130 and p107 may similarly induce dominant phenotypes. ..
  20. 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. ..
  21. Zhang C, Casas Tinto S, Li G, Lin N, Chung M, Moreno E, et al. An intergenic regulatory region mediates Drosophila Myc-induced apoptosis and blocks tissue hyperplasia. Oncogene. 2015;34:2385-97 pubmed publisher
    ..The epigenetic mechanisms controlling IRER accessibility appear to set thresholds for the P53- and dMyc-induced expression of apoptotic genes in vivo and may have a profound impact on cellular sensitivity to oncogene-induced stress. ..
  22. Liu W, Silverstein A, Shu H, Martinez B, Mumby M. A functional genomics analysis of the B56 isoforms of Drosophila protein phosphatase 2A. Mol Cell Proteomics. 2007;6:319-32 pubmed
    ..mts) or B56-2 subunit (wdb) of PP2A resulted in increased expression of the apoptotic inducers reaper and sickle. Co-knockdown of B56-1 with reaper, but not with sickle, reduced the apoptosis caused by depletion of the B56 ..
  23. Wichmann A, Jaklevic B, Su T. Ionizing radiation induces caspase-dependent but Chk2- and p53-independent cell death in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2006;103:9952-7 pubmed
    ..This work establishes Drosophila as a model for p53-independent apoptosis, which is of potential therapeutic importance for inducing cell death in p53-deficient cancer cells. ..
  24. Zhou L. The 'unique key' feature of the Iap-binding motifs in RHG proteins. Cell Death Differ. 2005;12:1148-51 pubmed
  25. Xu P, Guo M, Hay B. MicroRNAs and the regulation of cell death. Trends Genet. 2004;20:617-24 pubmed
  26. Brun S, Rincheval Arnold A, Colin J, Risler Y, Mignotte B, Guenal I. The myb-related gene stonewall induces both hyperplasia and cell death in Drosophila: rescue of fly lethality by coexpression of apoptosis inducers. Cell Death Differ. 2006;13:1752-62 pubmed
    ..Our results suggest that stwl(UY823) kills flies by causing inappropriate cell cycle entry, and that triggering the death of these overproliferating cells or slowing their proliferation restores viability. ..
  27. Lim Y, Hayashi S, Tsuda L. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons. PLoS ONE. 2012;7:e37028 pubmed publisher
    ..These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration. ..
  28. Zhang Y, Lin N, Carroll P, Chan G, Guan B, Xiao H, et al. Epigenetic blocking of an enhancer region controls irradiation-induced proapoptotic gene expression in Drosophila embryos. Dev Cell. 2008;14:481-93 pubmed publisher
    ..Thus, direct epigenetic regulation of two proapoptotic genes controls cellular sensitivity to cytotoxic stimuli. ..
  29. Mansilla A, Martín F, Martín D, Ferrús A. Ligand-independent requirements of steroid receptors EcR and USP for cell survival. Cell Death Differ. 2016;23:405-16 pubmed publisher
    ..These novel and context-dependent functional properties for EcR and USP receptors may help to understand the heterogeneous responses to steroid-based therapies in human pathologies. ..
  30. Zhang W, Cohen S. The Hippo pathway acts via p53 and microRNAs to control proliferation and proapoptotic gene expression during tissue growth. Biol Open. 2013;2:822-8 pubmed publisher
    ..These findings provide evidence that the Hippo pathway acts via several distinct routes to limit proliferation-induced apoptosis. ..
  31. Gaertner B, Johnston J, Chen K, Wallaschek N, Paulson A, Garruss A, et al. Poised RNA polymerase II changes over developmental time and prepares genes for future expression. Cell Rep. 2012;2:1670-83 pubmed publisher
    ..We compare our data with findings in mammalian embryonic stem cells and discuss a framework for predicting developmental programs on the basis of the chromatin state. ..
  32. Lee G, Sehgal R, Wang Z, Nair S, Kikuno K, Chen C, et al. Essential role of grim-led programmed cell death for the establishment of corazonin-producing peptidergic nervous system during embryogenesis and metamorphosis in Drosophila melanogaster. Biol Open. 2013;2:283-94 pubmed publisher
    ..combinatorial activities of four death genes, head involution defective (hid), reaper (rpr), grim, and sickle (skl), have been known to play crucial roles in the developmentally regulated programmed cell death (PCD) of ..
  33. Wing J, Schreader B, Yokokura T, Wang Y, Andrews P, Huseinovic N, et al. Drosophila Morgue is an F box/ubiquitin conjugase domain protein important for grim-reaper mediated apoptosis. Nat Cell Biol. 2002;4:451-6 pubmed
    ..Morgue may thus have a key function in apoptosis by targeting DIAP1 for ubiquitination and turnover. ..
  34. Gesellchen V, Boutros M. Managing the genome: microRNAs in Drosophila. Differentiation. 2004;72:74-80 pubmed
    ..Many of these recent experiments provide evidence that a systematic target discovery is feasible and that the biology of miRNAs can be functionally explored using forward and reverse genetic tools. ..
  35. Wildonger J, Sosinsky A, Honig B, Mann R. Lozenge directly activates argos and klumpfuss to regulate programmed cell death. Genes Dev. 2005;19:1034-9 pubmed
    ..These results provide novel insights into the control of programmed cell death (PCD) by Lz during Drosophila eye development. ..
  36. Ditzel M, Meier P. IAP degradation: decisive blow or altruistic sacrifice?. Trends Cell Biol. 2002;12:449-52 pubmed
  37. 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. ..
  38. Xia X, Holcik M. Strong eukaryotic IRESs have weak secondary structure. PLoS ONE. 2009;4:e4136 pubmed publisher
    ..The consistency in results between the yeast and the fruit fly suggests a possible shared mechanism of cap-independent translation initiation that relies on an unstructured RNA segment. ..
  39. Peterson J, Bass B, Jue D, Rodriguez A, Abrams J, McCall K. Noncanonical cell death pathways act during Drosophila oogenesis. Genesis. 2007;45:396-404 pubmed
    ..These results indicate that novel pathways must control PCD in the ovary. ..
  40. Lim Y, Yagi Y, Tsuda L. Cellular Defense and Sensory Cell Survival Require Distinct Functions of ebi in Drosophila. PLoS ONE. 2015;10:e0141457 pubmed publisher
    ..Our results offer clear in vivo evidence that the Ebi-containing co-repressor complex acts in a distinct manner to regulate transcription that is required for modulating the output of various processes during Drosophila development. ..
  41. Zhai Z, Fuchs A, Lohmann I. Cellular analysis of newly identified Hox downstream genes in Drosophila. Eur J Cell Biol. 2010;89:273-8 pubmed publisher
  42. 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. ..
  43. Lee G, Kikuno K, Nair S, Park J. Mechanisms of postecdysis-associated programmed cell death of peptidergic neurons in Drosophila melanogaster. J Comp Neurol. 2013;521:3972-91 pubmed publisher
    ..We found that grim functions as a principal death inducer, whereas other death genes, hid, reaper, and sickle, show no endogenous function...
  44. Lin N, Li X, Cui K, Chepelev I, Tie F, Liu B, et al. A barrier-only boundary element delimits the formation of facultative heterochromatin in Drosophila melanogaster and vertebrates. Mol Cell Biol. 2011;31:2729-41 pubmed publisher
    ..This suggests that the mechanism by which it functions to spatially restrict the formation of repressive chromatin marked by trimethylated H3K27 has also been conserved widely during evolution. ..
  45. Mehrotra S, Maqbool S, Kolpakas A, Murnen K, Calvi B. Endocycling cells do not apoptose in response to DNA rereplication genotoxic stress. Genes Dev. 2008;22:3158-71 pubmed publisher
    ..Similar mechanisms may operate during vertebrate development, with implications for cancer predisposition in certain tissues. ..
  46. Montero L, Müller N, Gallant P. Induction of apoptosis by Drosophila Myc. Genesis. 2008;46:104-11 pubmed publisher
    ..These data suggest that the control of apoptosis is a physiological function of Myc and that dMyc might play a role in the response to DNA damage. ..
  47. Igaki T, Miura M. Role of Bcl-2 family members in invertebrates. Biochim Biophys Acta. 2004;1644:73-81 pubmed
    ..The ancestral role of the Bcl-2 family protein may be pro-apoptotic, and the evolution of the functions of this family of proteins may be closely linked with the contribution of mitochondria to the cell death pathway. ..