Gene Symbol: 14-3-3epsilon
Description: 14-3-3epsilon
Alias: 14-3-3, 14-3-3 epsilon, 14-3-3-e, 14-3-3-epsilon, 14-3-30epsilon, 14-3-3EPSILON, 14-3-3e, 14-3-3omicron, 14.3.3 epsilon, 1433epsilon, 143E_DROME, CG31196, CT24092, D14-3-3e, D14-3-3epsilon, Dmel\CG31196, EK3-5, PAR-5, PAR5, Par-5, SR3-9, Su(Raf)3B, anon-WO0172774.141, anon-WO02059370.52, d14-3-3epsilon, e-14-3-3, eps, l(3)j2B10, par-5, 14-3-3epsilon, 14-3-3 epsilon, 14-3-3 protein epsilon, 14-3-3&epsilon, 14-3-3epsilon-PA, 14-3-3epsilon-PB, 14-3-3epsilon-PC, 14-3-3epsilon-PD, CG31196-PA, CG31196-PB, CG31196-PC, CG31196-PD, Tyrosine-3-monooxygenase, epsilon, suppressor of Ras85D 3-9
Species: fruit fly
Products:     14-3-3epsilon

Top Publications

  1. Su T, Parry D, Donahoe B, Chien C, O Farrell P, Purdy A. Cell cycle roles for two 14-3-3 proteins during Drosophila development. J Cell Sci. 2001;114:3445-54 pubmed
    Drosophila 14-3-3 epsilon and 14-3-3 zeta proteins have been shown to function in RAS/MAP kinase pathways that influence the differentiation of the adult eye and the embryo...
  2. Yano M, Nakamuta S, Wu X, Okumura Y, Kido H. A novel function of 14-3-3 protein: 14-3-3zeta is a heat-shock-related molecular chaperone that dissolves thermal-aggregated proteins. Mol Biol Cell. 2006;17:4769-79 pubmed
    ..Our observations provide the first direct evidence that a 14-3-3 protein functions as a stress-induced molecular chaperone that dissolves and renaturalizes thermal-aggregated proteins. ..
  3. Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford S, et al. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell. 2007;130:1120-33 pubmed
    ..These results uncover a universal size-control mechanism in metazoan. ..
  4. Benton R, St Johnston D. Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells. Cell. 2003;115:691-704 pubmed
    ..Thus, antagonism of Bazooka by PAR-1/14-3-3 may represent a general mechanism for establishing complementary cortical domains in polarized cells. ..
  5. Pellettieri J, Seydoux G. Anterior-posterior polarity in C. elegans and Drosophila--PARallels and differences. Science. 2002;298:1946-50 pubmed
    ..Although clear mechanistic parallels remain to be established, par-dependent regulation of microtubule dynamics and protein stability emerge as common themes. ..
  6. Karam C, Kellner W, Takenaka N, Clemmons A, Corces V. 14-3-3 mediates histone cross-talk during transcription elongation in Drosophila. PLoS Genet. 2010;6:e1000975 pubmed publisher
    ..These results suggest that 14-3-3 proteins mediate cross-talk between histone phosphorylation and acetylation at a critical step in transcription elongation. ..
  7. Przewloka M, Venkei Z, Bolanos Garcia V, Debski J, Dadlez M, Glover D. CENP-C is a structural platform for kinetochore assembly. Curr Biol. 2011;21:399-405 pubmed publisher
    ..Thus, the N-terminal part of Drosophila CENP-C is sufficient to recruit core kinetochore components and acts as the principal linkage between centromere and kinetochore during mitosis. ..
  8. Messaritou G, Grammenoudi S, Skoulakis E. Dimerization is essential for 14-3-3zeta stability and function in vivo. J Biol Chem. 2010;285:1692-700 pubmed publisher
    ..Finally, we present evidence suggesting endogenous homeostatic adjustment of the levels of the second family member in Drosophila, D14-3-3epsilon, to transgenic monomeric and dimerization-competent 14-3-3zeta. ..
  9. Nielsen M, Luo X, Biteau B, Syverson K, Jasper H. 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell. 2008;7:688-99 pubmed publisher
    ..Our results further show that increased expression of 14-3-3epsilon reverts FoxO-induced growth defects. 14-3-3epsilon thus serves as a central modulator of FoxO activity in the regulation of growth, cell death and longevity in vivo. ..

More Information


  1. Baas A, Smit L, Clevers H. LKB1 tumor suppressor protein: PARtaker in cell polarity. Trends Cell Biol. 2004;14:312-9 pubmed
    ..In this article, we summarize the findings regarding LKB1 over the past six years. In addition, we discuss LKB1 in polarity in the context of both the other PAR proteins and its tumor suppressive activities. ..
  2. Chang H, Rubin G. 14-3-3 epsilon positively regulates Ras-mediated signaling in Drosophila. Genes Dev. 1997;11:1132-9 pubmed
    We have isolated mutations in the gene encoding a Drosophila 14-3-3 epsilon protein as suppressors of the rough eye phenotype caused by the ectopic expression of RAS1(V12)...
  3. Karim F, Chang H, Therrien M, Wassarman D, Laverty T, Rubin G. A screen for genes that function downstream of Ras1 during Drosophila eye development. Genetics. 1996;143:315-29 pubmed
    ..At least two suppressors appear to function either between Ras1 and Raf or in parallel to Raf. ..
  4. Brodsky M, Sekelsky J, Tsang G, Hawley R, Rubin G. mus304 encodes a novel DNA damage checkpoint protein required during Drosophila development. Genes Dev. 2000;14:666-78 pubmed
    ..Similar mechanisms may account for the puzzling array of symptoms observed in humans with mutations in the ATM tumor suppressor gene. ..
  5. Shandala T, Woodcock J, Ng Y, Biggs L, Skoulakis E, Brooks D, et al. Drosophila 14-3-3? has a crucial role in anti-microbial peptide secretion and innate immunity. J Cell Sci. 2011;124:2165-74 pubmed publisher
    ..We conclude that 14-3-3? is required for Rab11-positive vesicle function, which in turn enables antimicrobial peptide secretion during an innate immune response. ..
  6. Kellner W, Ramos E, Van Bortle K, Takenaka N, Corces V. Genome-wide phosphoacetylation of histone H3 at Drosophila enhancers and promoters. Genome Res. 2012;22:1081-8 pubmed publisher
    ..Genome-wide analyses extend these conclusions to most Drosophila genes, showing that the presence of JIL-1, H3K9acS10ph, and H3K27acS28ph is a general feature of enhancers and promoters in this organism. ..
  7. Benton R, Palacios I, St Johnston D. Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation. Dev Cell. 2002;3:659-71 pubmed
    ..The C. elegans 14-3-3 protein, PAR-5, is also required for A-P polarization, suggesting that this is a conserved mechanism by which PAR-1 establishes cellular asymmetries. ..
  8. Oh H, Irvine K. In vivo regulation of Yorkie phosphorylation and localization. Development. 2008;135:1081-8 pubmed publisher
    ..These results identify modulation of subcellular localization as a mechanism of Yki regulation, and establish that this regulation occurs in vivo through multiple sites of Warts-dependent phosphorylation on Yki. ..
  9. Acevedo S, Tsigkari K, Grammenoudi S, Skoulakis E. In vivo functional specificity and homeostasis of Drosophila 14-3-3 proteins. Genetics. 2007;177:239-53 pubmed
    ..These results demonstrate functional differences both among Drosophila 14-3-3 proteins and between the two LEO isoforms in vivo, which likely underlie differential dimer affinities toward 14-3-3 targets. ..
  10. Lalle M, Leptourgidou F, Camerini S, Pozio E, Skoulakis E. Interkingdom complementation reveals structural conservation and functional divergence of 14-3-3 proteins. PLoS ONE. 2013;8:e78090 pubmed publisher
    ..duodenalis (g14-3-3), are consistent with this hypothesis, but whether g14-3-3 is functionally homologous to the epsilon isoforms is unknown...
  11. Dickson B, van der Straten A, Dominguez M, Hafen E. Mutations Modulating Raf signaling in Drosophila eye development. Genetics. 1996;142:163-71 pubmed
    ..We present the results of this screen in detail, as well as a preliminary genetic analysis of the six loci still to be characterized molecularly. ..
  12. Tsigkari K, Acevedo S, Skoulakis E. 14-3-3? Is required for germ cell migration in Drosophila. PLoS ONE. 2012;7:e36702 pubmed publisher
    ..We present evidence that D14-3-3? loss results in reduction or loss of the transcription factor Zfh-1, one of the main regulatory molecules of the pole cell migration, from the somatic gonad precursor cells. ..
  13. Shirasaki D, Greiner E, Al Ramahi I, Gray M, Boontheung P, Geschwind D, et al. Network organization of the huntingtin proteomic interactome in mammalian brain. Neuron. 2012;75:41-57 pubmed publisher
  14. Calero Cuenca F, Espinosa Vázquez J, Reina Campos M, Diaz Meco M, Moscat J, Sotillos S. Nuclear fallout provides a new link between aPKC and polarized cell trafficking. BMC Biol. 2016;14:32 pubmed publisher
    ..We propose a regulatory loop by which Nuf promotes aPKC apical recycling until sufficient levels of active aPKC are reached. Thus, we provide a novel link between cell polarity regulation and traffic control in epithelia. ..
  15. Chen X, Burgoyne R. Identification of common genetic modifiers of neurodegenerative diseases from an integrative analysis of diverse genetic screens in model organisms. BMC Genomics. 2012;13:71 pubmed publisher
  16. Chen C, Chien C. Negative regulation of atonal in proneural cluster formation of Drosophila R8 photoreceptors. Proc Natl Acad Sci U S A. 1999;96:5055-60 pubmed
    ..Taken together, these results suggest that a negative regulatory loop involving MAPK activation and Ato repression is required for the generation of evenly spaced proneural clusters. ..
  17. Temme C, Weissbach R, Lilie H, Wilson C, Meinhart A, Meyer S, et al. The Drosophila melanogaster Gene cg4930 Encodes a High Affinity Inhibitor for Endonuclease G. J Biol Chem. 2009;284:8337-48 pubmed publisher
    ..Flies homozygous for a hypomorphic EndoGI mutation have a strongly reduced viability, which is modulated by genetic background and diet. We propose that EndoGI protects the cell against low levels of EndoG outside mitochondria. ..
  18. Ren F, Zhang L, Jiang J. Hippo signaling regulates Yorkie nuclear localization and activity through 14-3-3 dependent and independent mechanisms. Dev Biol. 2010;337:303-12 pubmed publisher
    ..Finally, we provided evidence that Hpo signaling restricted Yki nuclear localization depending on CRM1-mediated nuclear export. ..
  19. Laflamme C, Galan J, Ben El Kadhi K, Méant A, Zeledon C, Carreno S, et al. Proteomics Screen Identifies Class I Rab11 Family Interacting Proteins as Key Regulators of Cytokinesis. Mol Cell Biol. 2017;37: pubmed publisher
    ..Together, our results suggest an evolutionarily conserved role for 14-3-3 in controlling Rip11-dependent protein transport during cytokinesis. ..
  20. Bergstralh D, Haack T, St Johnston D. Epithelial polarity and spindle orientation: intersecting pathways. Philos Trans R Soc Lond B Biol Sci. 2013;368:20130291 pubmed publisher
    ..In this review, we examine several factors implicated in both processes, namely Canoe, Bazooka, aPKC and Discs large, and consider the implications of this work on how the spindle is oriented during epithelial cell divisions. ..
  21. Tiebe M, Lutz M, De La Garza A, Buechling T, Boutros M, Teleman A. REPTOR and REPTOR-BP Regulate Organismal Metabolism and Transcription Downstream of TORC1. Dev Cell. 2015;33:272-84 pubmed publisher
    ..In vivo functional analysis using knockout flies reveals that REPTOR and REPTOR-BP play critical roles in maintaining energy homeostasis and promoting animal survival upon nutrient restriction. ..
  22. Lerner I, Bartok O, Wolfson V, Menet J, Weissbein U, Afik S, et al. Clk post-transcriptional control denoises circadian transcription both temporally and spatially. Nat Commun. 2015;6:7056 pubmed publisher
    ..Overall our results demonstrate a key role of Clk post-transcriptional control in stabilizing circadian transcription, which is essential for proper development and maintenance of circadian rhythms in Drosophila. ..
  23. Bornstein B, Zahavi E, Gelley S, Zoosman M, Yaniv S, Fuchs O, et al. Developmental Axon Pruning Requires Destabilization of Cell Adhesion by JNK Signaling. Neuron. 2015;88:926-940 pubmed publisher
    ..Taken together, we have uncovered a novel and unexpected interaction between the JNK pathway and cell adhesion and found that destabilization of cell adhesion is necessary for efficient pruning. ..
  24. Pflieger D, Jünger M, Muller M, Rinner O, Lee H, Gehrig P, et al. Quantitative proteomic analysis of protein complexes: concurrent identification of interactors and their state of phosphorylation. Mol Cell Proteomics. 2008;7:326-46 pubmed
  25. BARRON D, Kagey J. The role of the Hippo pathway in human disease and tumorigenesis. Clin Transl Med. 2014;3:25 pubmed publisher
    ..The common activation of YAP in many different tumor types provides an attractive target for potential therapeutic intervention. ..
  26. Wang C, Yao C, Li Y, Cai W, Bao X, Girton J, et al. Evidence against a role for the JIL-1 kinase in H3S28 phosphorylation and 14-3-3 recruitment to active genes in Drosophila. PLoS ONE. 2013;8:e62484 pubmed publisher
    ..Thus, our results argue strongly against a model where JIL-1 is required for H3S28 phosphorylation and 14-3-3 recruitment at active genes. ..
  27. Therrien M, Morrison D, Wong A, Rubin G. A genetic screen for modifiers of a kinase suppressor of Ras-dependent rough eye phenotype in Drosophila. Genetics. 2000;156:1231-42 pubmed
    ..One of them corresponds to the kismet locus, which encodes a putative chromatin remodeling factor. The relevance of these loci with respect to the function of KSR and the Ras1 pathway in general is discussed. ..
  28. Wehr M, Holder M, Gailite I, Saunders R, Maile T, Ciirdaeva E, et al. Salt-inducible kinases regulate growth through the Hippo signalling pathway in Drosophila. Nat Cell Biol. 2013;15:61-71 pubmed
    ..As Sik kinases have been implicated in nutrient sensing, this suggests a link between the Hpo pathway and systemic growth control. ..
  29. Tien A, Hsei H, Chien C. Dynamic expression and cellular localization of the drosophila 14-3-3epsilon during embryonic development. Mech Dev. 1999;81:209-12 pubmed
    ..During neuronal differentiation, the d14-3-3epsilon protein remained at a high level in the neuronal cytoplasm. ..
  30. Bharadwaj R, Roy M, Ohyama T, Sivan Loukianova E, Delannoy M, Lloyd T, et al. Cbl-associated protein regulates assembly and function of two tension-sensing structures in Drosophila. Development. 2013;140:627-38 pubmed publisher
  31. Follmer N, Wani A, Francis N. A polycomb group protein is retained at specific sites on chromatin in mitosis. PLoS Genet. 2012;8:e1003135 pubmed publisher
  32. Sekelsky J, Brodsky M, Burtis K. DNA repair in Drosophila: insights from the Drosophila genome sequence. J Cell Biol. 2000;150:F31-6 pubmed
  33. Lu M, Prehoda K. A NudE/14-3-3 pathway coordinates dynein and the kinesin Khc73 to position the mitotic spindle. Dev Cell. 2013;26:369-80 pubmed publisher
    ..The Khc73 stalk/14-3-3/NudE pathway defines a physical connection that coordinates the activities of multiple motor proteins to precisely position the spindle. ..
  34. Nakano A, Takashima S. LKB1 and AMP-activated protein kinase: regulators of cell polarity. Genes Cells. 2012;17:737-47 pubmed publisher
    ..Here, we review the mechanisms and factors responsible for organizing cell polarity and the role of LKB1 and AMPK in cell polarity. ..
  35. Teleman A, Chen Y, Cohen S. Drosophila Melted modulates FOXO and TOR activity. Dev Cell. 2005;9:271-81 pubmed
    ..We provide evidence that in the melted mutant, TOR activity is reduced and FOXO is activated. The melted mutant condition mimics the effects of nutrient deprivation in a normal animal, producing an animal with 40% less fat than normal. ..
  36. Margolis B, Borg J. Apicobasal polarity complexes. J Cell Sci. 2005;118:5157-9 pubmed
  37. Montembault E, Zhang W, Przewloka M, Archambault V, Sevin E, Laue E, et al. Nessun Dorma, a novel centralspindlin partner, is required for cytokinesis in Drosophila spermatocytes. J Cell Biol. 2010;191:1351-65 pubmed publisher
    ..Our findings indicate that Nesd is a novel carbohydrate-binding protein that functions together with centralspindlin in late cytokinesis, thus highlighting the importance of glycosylation in this process...
  38. Li J, Li W. Drosophila gain-of-function mutant RTK torso triggers ectopic Dpp and STAT signaling. Genetics. 2003;164:247-58 pubmed
    ..These results demonstrate an essential requirement of noncanonical signaling pathways for a persistently activated RTK to cause pathological defects in an organism. ..
  39. Ng Y, Sorvina A, Bader C, Weiland F, Lopez A, Hoffmann P, et al. Proteome Analysis of Drosophila Mutants Identifies a Regulatory Role for 14-3-3ε in Metabolic Pathways. J Proteome Res. 2017;16:1976-1987 pubmed publisher
    ..This study indicates that 14-3-3ε has a critical role in cellular metabolism involving either molecular crosstalk with the EcR or direct interaction with metabolic proteins. ..
  40. Partridge L, Alic N, Bjedov I, Piper M. Ageing in Drosophila: the role of the insulin/Igf and TOR signalling network. Exp Gerontol. 2011;46:376-81 pubmed publisher
    ..Reduced IIS can act acutely to lower death rate, implying that it may ameliorate the effects of ageing-related damage, rather than preventing it. ..
  41. Le T, Vuong L, Kim A, Hsu Y, Choi K. 14-3-3 proteins regulate Tctp-Rheb interaction for organ growth in Drosophila. Nat Commun. 2016;7:11501 pubmed publisher
    ..Growth defects from knockdown of 14-3-3 and Tctp are suppressed by CycE overexpression. This study suggests a novel mechanism of Tor regulation mediated by 14-3-3 interaction with Tctp and Rheb. ..
  42. Rubin G, Chang H, Karim F, Laverty T, Michaud N, Morrison D, et al. Signal transduction downstream from Ras in Drosophila. Cold Spring Harb Symp Quant Biol. 1997;62:347-52 pubmed
  43. Yang T, Terman J. 14-3-3? couples protein kinase A to semaphorin signaling and silences plexin RasGAP-mediated axonal repulsion. Neuron. 2012;74:108-21 pubmed publisher
    ..Our results indicate that these interactions switch repulsion to adhesion and identify a point of convergence for multiple guidance molecules. ..
  44. Lipinszki Z, Lefevre S, Savoian M, Singleton M, Glover D, Przewloka M. Centromeric binding and activity of Protein Phosphatase 4. Nat Commun. 2015;6:5894 pubmed publisher
    ..We also show that binding of Flfl to CENP-C is required to bring PP4 activity to centromeres to maintain CENP-C and attached core kinetochore proteins at chromosomes during mitosis. ..
  45. Wang S, Lu Y, Yin M, Wang C, Wu W, Li J, et al. Importin α1 Mediates Yorkie Nuclear Import via an N-terminal Non-canonical Nuclear Localization Signal. J Biol Chem. 2016;291:7926-37 pubmed publisher
    ..Taken together, we identified a potential nuclear localization signal at the N-terminal end of Yorkie as well as a critical role for Importin α1 in Yorkie nuclear import. ..
  46. Walworth N. Cell-cycle checkpoint kinases: checking in on the cell cycle. Curr Opin Cell Biol. 2000;12:697-704 pubmed
    ..In addition, an appreciation that DNA damage arises as a natural consequence of cellular metabolism, including DNA replication itself, has influenced thinking regarding the nature of checkpoint pathways. ..
  47. Chen H, Fernandez Funez P, Acevedo S, Lam Y, Kaytor M, Fernandez M, et al. Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1. Cell. 2003;113:457-68 pubmed
    ..Our finding that phosphatidylinositol 3-kinase/Akt signaling and 14-3-3 cooperate to modulate the neurotoxicity of ataxin-1 provides insight into SCA1 pathogenesis and identifies potential targets for therapeutic intervention. ..
  48. Krahn M, Egger Adam D, Wodarz A. PP2A antagonizes phosphorylation of Bazooka by PAR-1 to control apical-basal polarity in dividing embryonic neuroblasts. Dev Cell. 2009;16:901-8 pubmed publisher
    ..Overexpression of PAR-1 or Baz, or mutation of 14-3-3 proteins that bind phosphorylated Baz, causes essentially the same phenotype, indicating that the balance of PAR-1 and PP2A effects on Baz phosphorylation determines NB polarity. ..
  49. Oh H, Irvine K. In vivo analysis of Yorkie phosphorylation sites. Oncogene. 2009;28:1916-27 pubmed publisher
    ..We also identify two potential sites of phosphorylation by an unknown kinase, which could influence phosphorylation of Ser168 by Wts, suggesting that there are additional mechanisms for regulating Yki/YAP activity. ..
  50. Ahringer J. Control of cell polarity and mitotic spindle positioning in animal cells. Curr Opin Cell Biol. 2003;15:73-81 pubmed
    ..Microtubules and conserved PAR proteins are essential mediators of cell polarity, and mitotic spindle positioning depends on heterotrimeric G protein signalling and the microtubule motor protein dynein. ..
  51. Glatter T, Schittenhelm R, Rinner O, Roguska K, Wepf A, Jünger M, et al. Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome. Mol Syst Biol. 2011;7:547 pubmed publisher
    ..Subsequent genetic studies in flies suggest a role for dTTT in controlling cell growth via a dTORC1- and dTORC2-dependent mechanism. ..
  52. Xu K, Zheng X, Sehgal A. Regulation of feeding and metabolism by neuronal and peripheral clocks in Drosophila. Cell Metab. 2008;8:289-300 pubmed publisher
    ..We propose that the input of neuronal clocks and clocks in metabolic tissues is coordinated to provide effective energy homeostasis...
  53. Wang P, Galan J, Normandin K, Bonneil E, Hickson G, Roux P, et al. Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression. J Cell Biol. 2013;202:277-93 pubmed publisher
    ..We show that the nucleo-cytoplasmic regulation of Gwl is essential for its functions in vivo and propose that the spatial regulation of Gwl at mitotic entry contributes to the mitotic switch. ..
  54. Yang Y, Zhan L, Zhang W, Sun F, Wang W, Tian N, et al. RNA secondary structure in mutually exclusive splicing. Nat Struct Mol Biol. 2011;18:159-68 pubmed publisher
    ..Our findings suggest a broadly applicable mechanism to ensure mutually exclusive splicing. ..