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Gene Review

14-3-3zeta  -  CG17870 gene product from transcript...

Drosophila melanogaster

Synonyms: 14-3-3, 14-3-3 protein zeta, 14-3-3 zeta, 14-3-3-like protein, 14-3-3-zeta, ...
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Disease relevance of 14-3-3zeta

  • We have observed that, in Drosophila cells, the 14-3-3zeta is up-regulated under heat stress conditions, a process mediated by a heat shock transcription factor [1].

Psychiatry related information on 14-3-3zeta

  • Because strong mutations in this gene are lethal, we investigated the nature of the defects that precipitate the learning and memory deficit and the role of the two protein isoforms encoded by leonardo in these processes [2].
  • The prevalence of functional 14-3-3 binding sites throughout the proteome, and especially among growth factor receptors and signaling molecules, reflects a global role for 14-3-3 in multiple cellular decision making [3].

High impact information on 14-3-3zeta


Biological context of 14-3-3zeta


Anatomical context of 14-3-3zeta


Associations of 14-3-3zeta with chemical compounds


Physical interactions of 14-3-3zeta

  • Coimmunoprecipitation experiments from Drosophila heads and transfected cells confirm that 14-3-3 interacts with dSlo via Slob [13].
  • The results provide evidence for a dSlo/Slob/14-3-3 regulatory protein complex [13].

Regulatory relationships of 14-3-3zeta

  • We find that, in the absence of Tor, overexpression of leo is sufficient to activate tll expression [14].
  • Slob binds to and modulates the Drosophila Slowpoke (dSlo) calcium-activated potassium channel and also recruits the ubiquitous signaling protein 14-3-3 to the channel regulatory complex [15].

Other interactions of 14-3-3zeta

  • These data, taken together, suggest that monomeric D14-3-3zeta is capable of modulating dSlo channel activity in this regulatory complex [6].
  • A yeast two-hybrid screen with Slob as bait identifies the zeta isoform of 14-3-3 as a Slob-binding protein [13].
  • 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 [8].
  • Revisiting three paradigmatic mutations altering olfactory learning and memory in Drosophila (dunce, leonardo, amnesiac) a link was established between each mutation and the operation of VDICs in Kenyon cells, the intrinsic neurons of the mushroom bodies (MBs) [16].
  • These results suggest that the increased kinase activity of mutant D-Raf is caused by the selective loss of 14-3-3 binding to its amino terminus [17].

Analytical, diagnostic and therapeutic context of 14-3-3zeta

  • Sequence analysis reveals that the cDNA-encoded protein shares 84% identity with the rat, human or sheep 14-3-3zeta isoform, and between 66% and 77% identity with bovine, human or rat beta, bovine gamma, human tau, Drosophila 14-3-3 and a previously isolated Xenopus member [18].
  • Microinjection experiments showed a requirement for 14-3-3 function in mesodermal specification [19].


  1. A Novel Function of 14-3-3 Protein: 14-3-3{zeta} Is a Heat-Shock-related Molecular Chaperone That Dissolves Thermal-aggregated Proteins. Yano, M., Nakamuta, S., Wu, X., Okumura, Y., Kido, H. Mol. Biol. Cell (2006) [Pubmed]
  2. Conditional rescue of olfactory learning and memory defects in mutants of the 14-3-3zeta gene leonardo. Philip, N., Acevedo, S.F., Skoulakis, E.M. J. Neurosci. (2001) [Pubmed]
  3. 14-3-3 protein signaling in development and growth factor responses. Thomas, D., Guthridge, M., Woodcock, J., Lopez, A. Curr. Top. Dev. Biol. (2005) [Pubmed]
  4. Requirement for Drosophila 14-3-3 zeta in Raf-dependent photoreceptor development. Kockel, L., Vorbrüggen, G., Jäckle, H., Mlodzik, M., Bohmann, D. Genes Dev. (1997) [Pubmed]
  5. Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding. Rittinger, K., Budman, J., Xu, J., Volinia, S., Cantley, L.C., Smerdon, S.J., Gamblin, S.J., Yaffe, M.B. Mol. Cell (1999) [Pubmed]
  6. Monomeric 14-3-3 protein is sufficient to modulate the activity of the Drosophila slowpoke calcium-dependent potassium channel. Zhou, Y., Reddy, S., Murrey, H., Fei, H., Levitan, I.B. J. Biol. Chem. (2003) [Pubmed]
  7. Olfactory learning deficits in mutants for leonardo, a Drosophila gene encoding a 14-3-3 protein. Skoulakis, E.M., Davis, R.L. Neuron (1996) [Pubmed]
  8. Cell cycle roles for two 14-3-3 proteins during Drosophila development. Su, T.T., Parry, D.H., Donahoe, B., Chien, C.T., O'Farrell, P.H., Purdy, A. J. Cell. Sci. (2001) [Pubmed]
  9. Leonardo, a Drosophila 14-3-3 protein involved in learning, regulates presynaptic function. Broadie, K., Rushton, E., Skoulakis, E.M., Davis, R.L. Neuron (1997) [Pubmed]
  10. 14-3-3 protein regulation of proton pumps and ion channels. Bunney, T.D., van den Wijngaard, P.W., de Boer, A.H. Plant Mol. Biol. (2002) [Pubmed]
  11. Characterization of a Drosophila melanogaster gene similar to the mammalian genes encoding the tyrosine/tryptophan hydroxylase activator and protein kinase C inhibitor proteins. Swanson, K.D., Ganguly, R. Gene (1992) [Pubmed]
  12. Role of 14-3-3 proteins in eukaryotic signaling and development. Darling, D.L., Yingling, J., Wynshaw-Boris, A. Curr. Top. Dev. Biol. (2005) [Pubmed]
  13. A dynamically regulated 14-3-3, Slob, and Slowpoke potassium channel complex in Drosophila presynaptic nerve terminals. Zhou, Y., Schopperle, W.M., Murrey, H., Jaramillo, A., Dagan, D., Griffith, L.C., Levitan, I.B. Neuron (1999) [Pubmed]
  14. The Drosophila 14-3-3 protein Leonardo enhances Torso signaling through D-Raf in a Ras 1-dependent manner. Li, W., Skoulakis, E.M., Davis, R.L., Perrimon, N. Development (1997) [Pubmed]
  15. Expression and function of variants of slob, slowpoke channel binding protein, in Drosophila. Jaramillo, A.M., Zeng, H., Fei, H., Zhou, Y., Levitan, I.B. J. Neurophysiol. (2006) [Pubmed]
  16. Bridging behavior and physiology: Ion-channel perspective on mushroom body-dependent olfactory learning and memory in Drosophila. Gasque, G., Labarca, P., Delgado, R., Darszon, A. J. Cell. Physiol. (2006) [Pubmed]
  17. Negative regulation of Raf activity by binding of 14-3-3 to the amino terminus of Raf in vivo. Rommel, C., Radziwill, G., Moelling, K., Hafen, E. Mech. Dev. (1997) [Pubmed]
  18. Sequence and expression analysis of a Xenopus laevis cDNA which encodes a homologue of mammalian 14-3-3 zeta protein. Kousteni, S., Tura, F., Sweeney, G.E., Ramji, D.P. Gene (1997) [Pubmed]
  19. Role of 14-3-3 proteins in early Xenopus development. Wu, C., Muslin, A.J. Mech. Dev. (2002) [Pubmed]
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