Gene Symbol: Ywhae
Description: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon
Alias: 14-3-3e, 14-3-3 protein epsilon, 14-3-3 epsilon, MSF L, mitochondrial import stimulation factor (MSF) L subunit, mitochondrial import stimulation factor L subunit, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activatioprotein epsilon polypeptide
Species: rat
Products:     Ywhae

Top Publications

  1. Wu J, Cheung W, Tsai Y, Chen Y, Fong W, Tsai H, et al. Ligand-activated peroxisome proliferator-activated receptor-gamma protects against ischemic cerebral infarction and neuronal apoptosis by 14-3-3 epsilon upregulation. Circulation. 2009;119:1124-34 pubmed publisher
    ..14-3-3epsilon Upregulation enhances sequestration of phosphorylated Bad and thereby suppresses apoptosis. ..
  2. Kim A, Puram S, Bilimoria P, Ikeuchi Y, Keough S, Wong M, et al. A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons. Cell. 2009;136:322-36 pubmed publisher
    ..The identification of a centrosomal Cdc20-APC ubiquitin signaling pathway holds important implications for diverse biological processes, including neuronal connectivity and plasticity. ..
  3. Meng J, Cui C, Liu Y, Jin M, Wu D, Liu C, et al. The role of 14-3-3? interaction with phosphorylated Cdc25B at its Ser321 in the release of the mouse oocyte from prophase I arrest. PLoS ONE. 2013;8:e53633 pubmed publisher
    ..Taken together, these data indicate that Ser321 of Cdc25B is the specific binding site for 14-3-3? binding, and that 14-3-3? is the significant factor in Cdc25B regulation during meiotic resumption of GV stage. ..
  4. Roseboom P, Weller J, Babila T, Aitken A, Sellers L, Moffett J, et al. Cloning and characterization of the epsilon and zeta isoforms of the 14-3-3 proteins. DNA Cell Biol. 1994;13:629-40 pubmed
    ..This investigation also revealed the epsilon isoform was present at high levels in the rat pineal gland early in development and decreased steadily thereafter and that 30-kD isoforms exhibited the inverse developmental pattern. ..
  5. Sai Y, Peng K, Ye F, Zhao X, Zhao Y, Zou Z, et al. 14-3-3 Proteins in the regulation of rotenone-induced neurotoxicity might be via its isoform 14-3-3epsilon's involvement in autophagy. Cell Mol Neurobiol. 2013;33:1109-21 pubmed publisher
  6. Wang X, Grammatikakis N, Siganou A, Calderwood S. Regulation of molecular chaperone gene transcription involves the serine phosphorylation, 14-3-3 epsilon binding, and cytoplasmic sequestration of heat shock factor 1. Mol Cell Biol. 2003;23:6013-26 pubmed
    ..Our experiments indicate a novel pathway for HSF1 regulation and suggest a mechanism for suppression of its activity during cellular proliferation. ..
  7. Toyo oka K, Shionoya A, Gambello M, Cardoso C, Leventer R, Ward H, et al. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet. 2003;34:274-85 pubmed
    ..Here, we show that the gene encoding 14-3-3epsilon (YWHAE), one of a family of ubiquitous phosphoserine/threonine-binding proteins, is always deleted in individuals with ..
  8. Chang K, Vincent F, Shah K. Deregulated Cdk5 triggers aberrant activation of cell cycle kinases and phosphatases inducing neuronal death. J Cell Sci. 2012;125:5124-37 pubmed publisher
  9. Barbash O, Lee E, Diehl J. Phosphorylation-dependent regulation of SCF(Fbx4) dimerization and activity involves a novel component, 14-3-3?. Oncogene. 2011;30:1995-2002 pubmed publisher
    ..Collectively, the current results suggest a model wherein 14-3-3? binds to Ser12-phosphorylated Fbx4 to mediate dimerization and function. ..

More Information


  1. Grozinger C, Schreiber S. Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization. Proc Natl Acad Sci U S A. 2000;97:7835-40 pubmed
    ..Regulation of the cellular localization of HDAC4 and HDAC5 by 14-3-3 represents a mechanism for controlling the transcriptional activity of these class II HDAC proteins. ..
  2. Suginta W, Karoulias N, Aitken A, Ashley R. Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms. Biochem J. 2001;359:55-64 pubmed
    ..Our results provide the basis for new hypotheses concerning novel ways in which CLIC proteins might be associated with cell membrane remodelling, the control of cell shape, and anion channel activity. ..
  3. Du J, Liao W, Wang Y, Han C, Zhang Y. Inhibitory effect of 14-3-3 proteins on serum-induced proliferation of cardiac fibroblasts. Eur J Cell Biol. 2005;84:843-52 pubmed
    ..Collectively, these findings reveal that the expression of 14-3-3 epsilon can be upregulated by serum in CFs and 14-3-3s may exert an inhibitory effect on serum-induced proliferation. ..
  4. Taya S, Shinoda T, Tsuboi D, Asaki J, Nagai K, Hikita T, et al. DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1. J Neurosci. 2007;27:15-26 pubmed
    ..Furthermore, the knockdown of NUDEL or LIS1 inhibited axon elongation. Together, these results indicate that DISC1 regulates the localization of NUDEL/LIS1/14-3-3epsilon complex into the axons as a cargo receptor for axon elongation. ..
  5. Alam R, Hachiya N, Sakaguchi M, Kawabata S, Iwanaga S, Kitajima M, et al. cDNA cloning and characterization of mitochondrial import stimulation factor (MSF) purified from rat liver cytosol. J Biochem. 1994;116:416-25 pubmed
    ..Identification of MSF as 14-3-3 proteins establishes a novel function for this family of proteins and indicates their role as cytosolic chaperones to aid many important cellular events. ..
  6. Puram S, Kim A, Ikeuchi Y, Wilson Grady J, Merdes A, Gygi S, et al. A CaMKII? signaling pathway at the centrosome regulates dendrite patterning in the brain. Nat Neurosci. 2011;14:973-83 pubmed publisher
    ..Our findings define a new, isoform-specific function for CaMKII? that regulates ubiquitin signaling at the centrosome and thereby orchestrates dendrite patterning, with important implications for neuronal connectivity in the brain. ..
  7. Ichimura T, Yamamura H, Sasamoto K, Tominaga Y, Taoka M, Kakiuchi K, et al. 14-3-3 proteins modulate the expression of epithelial Na+ channels by phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase. J Biol Chem. 2005;280:13187-94 pubmed
    ..Our findings suggest that 14-3-3 proteins modulate the cell surface density of ENaC cooperatively with Sgk1 kinase by maintaining hNedd4-2 in an inactive phosphorylated state. ..
  8. Kagan A, Melman Y, Krumerman A, McDonald T. 14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity. EMBO J. 2002;21:1889-98 pubmed
    ..The net result is a prolongation of the effect of adrenergic stimulation upon HERG activity. Thus, 14-3-3 interactions with HERG may provide a unique mechanism for plasticity in the control of membrane excitability and cardiac rhythm. ..
  9. Eilers A, Sundwall E, Lin M, Sullivan A, Ayer D. A novel heterodimerization domain, CRM1, and 14-3-3 control subcellular localization of the MondoA-Mlx heterocomplex. Mol Cell Biol. 2002;22:8514-26 pubmed
    ..Second, an extracellular signal(s) must overcome the cytoplasmic localization function imparted by CRM1 and 14-3-3 binding to the N terminus of MondoA. ..
  10. Schindler C, Heverin M, Henshall D. Isoform- and subcellular fraction-specific differences in hippocampal 14-3-3 levels following experimentally evoked seizures and in human temporal lobe epilepsy. J Neurochem. 2006;99:561-9 pubmed
  11. Kurz E, Leader K, Kroll D, Clark M, Gieseler F. Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. J Biol Chem. 2000;275:13948-54 pubmed
    ..The association of topo II with 14-3-3 proteins does not extend to all 14-3-3 isoforms. No protein interaction or disruption of topo II function was observed with 14-3-3final sigma. ..
  12. Clokie S, Falconer H, Mackie S, Dubois T, Aitken A. The interaction between casein kinase Ialpha and 14-3-3 is phosphorylation dependent. FEBS J. 2009;276:6971-84 pubmed publisher
    ..We also show that both fission and budding yeast CKI kinase homologues phosphorylate mammalian and budding yeast (BMH1 and BMH2) 14-3-3 at the equivalent site. ..
  13. Hagemann C, Patel R, Blank J. MEKK3 interacts with the PA28 gamma regulatory subunit of the proteasome. Biochem J. 2003;373:71-9 pubmed
    ..MEKK3 represents the first protein kinase capable of binding and phosphorylating a PA, and provides a potential mechanism to link stress-activated protein kinase signalling with the PA28 gamma-dependent proteasome. ..
  14. Gao L, Gu X, Yu D, Yu R, Zeng G. Association of a 14-3-3 protein with CMP-NeuAc:GM1 alpha 2,3-sialyltransferase. Biochem Biophys Res Commun. 1996;224:103-7 pubmed
  15. Linde C, Di Leva F, Domi T, Tosatto S, Brini M, Carafoli E. Inhibitory interaction of the 14-3-3 proteins with ubiquitous (PMCA1) and tissue-specific (PMCA3) isoforms of the plasma membrane Ca2+ pump. Cell Calcium. 2008;43:550-61 pubmed
  16. Surgucheva I, Shestopalov V, Surguchov A. Effect of gamma-synuclein silencing on apoptotic pathways in retinal ganglion cells. J Biol Chem. 2008;283:36377-85 pubmed publisher
    ..Lowering Syn G causes Bad dephosphorylation, dissociation from phosphorylated 14-3-3, and translocation to mitochondria where it initiates apoptotic death cascade. ..
  17. Yang X, Lee W, Sobott F, Papagrigoriou E, Robinson C, Grossmann J, et al. Structural basis for protein-protein interactions in the 14-3-3 protein family. Proc Natl Acad Sci U S A. 2006;103:17237-42 pubmed
    ..These results show that the 14-3-3 proteins are adaptable structures in which internal flexibility is likely to facilitate recognition and binding of their interaction partners. ..
  18. Harrison B, Roberts C, Hood D, Sweeney M, Gould J, Bush E, et al. The CRM1 nuclear export receptor controls pathological cardiac gene expression. Mol Cell Biol. 2004;24:10636-49 pubmed
    ..Pharmacological approaches targeting CRM1-dependent nuclear export in heart muscle may have salutary effects on cardiac function by suppressing maladaptive changes in gene expression evoked by stress signals. ..
  19. Stewart S, Sundaram M, Zhang Y, Lee J, Han M, Guan K. Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization. Mol Cell Biol. 1999;19:5523-34 pubmed
    ..Together, these results suggest that KSR may act as a scaffolding protein for the Ras-mitogen-activated protein kinase pathway. ..
  20. Nakano K, Chen J, Tarr G, Yoshida T, Flynn J, Bitensky M. Rethinking the role of phosducin: light-regulated binding of phosducin to 14-3-3 in rod inner segments. Proc Natl Acad Sci U S A. 2001;98:4693-8 pubmed
    ..By dissociating the Pd/14-3-3 complex, light enables both proteins to function in this role. ..
  21. Pulina M, Rizzuto R, Brini M, Carafoli E. Inhibitory interaction of the plasma membrane Na+/Ca2+ exchangers with the 14-3-3 proteins. J Biol Chem. 2006;281:19645-54 pubmed
    ..In vitro binding experiments revealed that all three NCX isoforms interacted with multiple 14-3-3 isoforms. 14-3-3 was bound by both phosphorylated and nonphosphorylated NCX, but the phosphorylated form had much higher binding affinity. ..
  22. Efendiev R, Chen Z, Krmar R, Uhles S, Katz A, Pedemonte C, et al. The 14-3-3 protein translates the NA+,K+-ATPase {alpha}1-subunit phosphorylation signal into binding and activation of phosphoinositide 3-kinase during endocytosis. J Biol Chem. 2005;280:16272-7 pubmed
    ..Thus, the 14-3-3 protein represents a critical linking mechanism for recruiting phosphoinositide 3-kinase to the site of Na(+),K(+)-ATPase endocytosis. ..
  23. Wang J, Bai X, Chen Y, Zhao Y, Liu X. Homocysteine induces apoptosis of rat hippocampal neurons by inhibiting 14-3-3? expression and activating calcineurin. PLoS ONE. 2012;7:e48247 pubmed publisher
    ..These findings demonstrated that calcineurin activation and downregulation of 14-3-3? may be one of the mechanisms of Hcy-induced apoptosis of hippocampal neurons. ..
  24. Puram S, Kim A, Park H, Anckar J, Bonni A. The ubiquitin receptor S5a/Rpn10 links centrosomal proteasomes with dendrite development in the mammalian brain. Cell Rep. 2013;4:19-30 pubmed publisher
    ..Together, our findings define a function for a specific pool of proteasomes at the neuronal centrosome and identify a biological function for S5a/Rpn10 in the mammalian brain. ..