Gene Symbol: Ywhaz
Description: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Alias: 14-3-3z, 14-3-3 protein zeta/delta, KCIP-1, mitochondrial import stimulation factor S1 subunit, protein kinase C inhibitor protein 1, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide
Species: rat
Products:     Ywhaz

Top Publications

  1. Sadik G, Tanaka T, Kato K, Yamamori H, Nessa B, Morihara T, et al. Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein: implications for the mechanism of tau aggregation. J Neurochem. 2009;108:33-43 pubmed publisher
    ..Also as the phosphorylation at Ser214 is up-regulated in Alzheimer's disease brain, tau's interaction with 14-3-3 might be involved in the pathology of this disease. ..
  2. Zhou J, Shao Z, Kerkela R, Ichijo H, Muslin A, Pombo C, et al. Serine 58 of 14-3-3zeta is a molecular switch regulating ASK1 and oxidant stress-induced cell death. Mol Cell Biol. 2009;29:4167-76 pubmed publisher
    ..Our findings identify a novel pathway that regulates ASK1 activation and oxidant stress-induced cell death. ..
  3. Baik S, Jung K, Choi M, Yang B, Kim S, Lee J, et al. Fluoxetine-induced up-regulation of 14-3-3zeta and tryptophan hydroxylase levels in RBL-2H3 cells. Neurosci Lett. 2005;374:53-7 pubmed
    ..This suggests that the 14-3-3zeta and TPH genes may play a role in the molecular mechanism of fluoxetine. To date, no cases of 14-3-3zeta alterations by antidepressants and specifically by fluoxetine have been reported. ..
  4. Danis O, Demir S, Günel A, Aker R, Gülçebi M, Onat F, et al. Changes in intracellular protein expression in cortex, thalamus and hippocampus in a genetic rat model of absence epilepsy. Brain Res Bull. 2011;84:381-8 pubmed publisher
    ..These results indicate that not only membrane proteins but also cytoplasmic proteins may take place in the pathophysiology and can be therapeutic targets in absence epilepsy. ..
  5. 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. ..
  6. Birkenfeld J, Kartmann B, Anliker B, Ono K, Schlötcke B, Betz H, et al. Characterization of zetin 1/rBSPRY, a novel binding partner of 14-3-3 proteins. Biochem Biophys Res Commun. 2003;302:526-33 pubmed
    ..Our results suggest a role for zetin 1/rBSPRY-14-3-3 interactions at specialized submembrane domains. ..
  7. Chen J, Lee C, Errico S, Becker K, Freed W. Increases in expression of 14-3-3 eta and 14-3-3 zeta transcripts during neuroprotection induced by delta9-tetrahydrocannabinol in AF5 cells. J Neurosci Res. 2007;85:1724-33 pubmed
    ..The 14-3-3 eta (14-3-3eta; gene symbol Ywhah) and 14-3-3 zeta (14-3-3zeta; gene symbol Ywhaz) transcripts were deceased by NMDA treatment and increased by THC treatment prior to NMDA, as measured by cDNA ..
  8. Fidalgo M, Fraile M, Pires A, Force T, Pombo C, Zalvide J. CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation. J Cell Sci. 2010;123:1274-84 pubmed publisher
    ..Our findings suggest that Golgi dysfunction and the ensuing abnormalities of cell orientation and migration resulting from CCM3 mutations contribute to CCM pathogenesis. ..
  9. Thompson S, Pearson A, Ashley M, Jessick V, Murphy B, GAFKEN P, et al. Identification of a novel Bcl-2-interacting mediator of cell death (Bim) E3 ligase, tripartite motif-containing protein 2 (TRIM2), and its role in rapid ischemic tolerance-induced neuroprotection. J Biol Chem. 2011;286:19331-9 pubmed publisher
    ..Taken together, these data support a role for TRIM2 in mediating the p42/p44 MAPK-dependent ubiquitination of Bim in rapid ischemic tolerance. ..

More Information


  1. van der Brug M, Goodenough S, Wilce P. Kainic acid induces 14-3-3 zeta expression in distinct regions of rat brain. Brain Res. 2002;956:110-5 pubmed
    ..The increase gene expression of 14-3-3 zeta represents a transcription-mediated response associated with region selective neuronal damage induced by kainic acid. ..
  2. Berggreen C, Henriksson E, Jones H, Morrice N, Göransson O. cAMP-elevation mediated by ?-adrenergic stimulation inhibits salt-inducible kinase (SIK) 3 activity in adipocytes. Cell Signal. 2012;24:1863-71 pubmed publisher
    ..Our findings of cAMP-mediated regulation of SIK3 suggest that SIK3 may mediate some of the effects of this important second messenger in adipocytes. ..
  3. 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. ..
  4. Lai X, Wang J, Nabar N, Pan S, Tang C, Huang Y, et al. Proteomic response to acupuncture treatment in spontaneously hypertensive rats. PLoS ONE. 2012;7:e44216 pubmed publisher
    ..heat shock protein-90, synapsin-1, pyruvate kinase isozyme, NAD-dependent deacetylase sirtuin-2, protein kinase C inhibitor protein 1, ubiquitin hydrolase isozyme L1, and myelin basic protein...
  5. Wu L, Wei X, Fan Y, Miao J, Wang L, Zhang Y, et al. Altered expression of 14-3-3? protein in spinal cords of rat fetuses with spina bifida aperta. PLoS ONE. 2013;8:e70457 pubmed publisher
  6. Neasta J, Kiely P, He D, Adams D, O Connor R, Ron D. Direct interaction between scaffolding proteins RACK1 and 14-3-3? regulates brain-derived neurotrophic factor (BDNF) transcription. J Biol Chem. 2012;287:322-36 pubmed publisher
    ..As RACK1 and 14-3-3? are two multifunctional scaffolding proteins that coordinate a wide variety of signaling events, their interaction is likely to regulate other essential cellular functions. ..
  7. Fujii T, Ueeda T. Stimulation of 14-3-3 protein and its isoform on histamine secretion from permeabilized rat peritoneal mast cells. Biol Pharm Bull. 2002;25:1524-7 pubmed
    ..PD 98059, however, had little effect on the histamine release. These results suggest the possibility that 14-3-3zeta is associated with signal transduction for degranulation of the mast cells. ..
  8. Lim R, Winteringham L, Williams J, McCulloch R, Ingley E, Tiao J, et al. MADM, a novel adaptor protein that mediates phosphorylation of the 14-3-3 binding site of myeloid leukemia factor 1. J Biol Chem. 2002;277:40997-1008 pubmed
    ..In summary, this study has identified two partner proteins of Mlf1 that may influence its subcellular localization and biological function. ..
  9. 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
  10. Gouraud S, Yao S, Heesom K, Paton J, Murphy D. 14-3-3 proteins within the hypothalamic-neurohypophyseal system of the osmotically stressed rat: transcriptomic and proteomic studies. J Neuroendocrinol. 2007;19:913-22 pubmed
    ..Microarray studies on mRNAs differentially expressed in the SON revealed that transcripts encoding the Ywhag and Ywhaz isoforms of the 14-3-3 family of regulatory proteins, are increased in the rat SON by 3 days of water deprivation; ..
  11. Wang J, Lou H, Pedersen C, Smith A, Perez R. 14-3-3zeta contributes to tyrosine hydroxylase activity in MN9D cells: localization of dopamine regulatory proteins to mitochondria. J Biol Chem. 2009;284:14011-9 pubmed publisher
  12. Gu Y, Jin Y, Choi J, Baek K, Yeo C, Lee K. Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon. FEBS Lett. 2006;580:305-10 pubmed
    ..Therefore, our results suggest that PKA is a new member of protein kinases that can phosphorylate and impair the function of 14-3-3. ..
  13. Cavalcante A, Siqueira R, Araujo J, Gondim D, Ribeiro R, Quetz J, et al. Role of NMDA receptors in the trigeminal pathway, and the modulatory effect of magnesium in a model of rat temporomandibular joint arthritis. Eur J Oral Sci. 2013;121:573-83 pubmed publisher
    ..The present results may lead to a better understanding of central processing in the nociceptive trigeminal pathway and the development of new approaches to treat orofacial pain with a TMJ origin. ..
  14. Qureshi H, Han D, MacDonald R, Paudel H. Overexpression of 14-3-3z promotes tau phosphorylation at Ser262 and accelerates proteosomal degradation of synaptophysin in rat primary hippocampal neurons. PLoS ONE. 2013;8:e84615 pubmed publisher
    ..Synaptophysin is involved in synapse formation and neurotransmitter release. Our results suggest that 14-3-3z may cause synaptic pathology by reducing synaptophysin levels in the brains of patients suffering from AD. ..
  15. Hansraj N, Xiao L, Wu J, Chen G, Turner D, Wang J, et al. Posttranscriptional regulation of 14-3-3? by RNA-binding protein HuR modulating intestinal epithelial restitution after wounding. Physiol Rep. 2016;4: pubmed publisher
    ..These results indicate that HuR induces 14-3-3? translation via interaction with its 3' UTR and that 14-3-3? is necessary for stimulation of IEC migration after wounding. ..
  16. 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. ..
  17. Obsilova V, Vecer J, Herman P, Pabianova A, Sulc M, Teisinger J, et al. 14-3-3 Protein interacts with nuclear localization sequence of forkhead transcription factor FoxO4. Biochemistry. 2005;44:11608-17 pubmed
    ..Our results also suggest that the DNA-binding domain of FoxO4 remains relatively mobile while bound to the 14-3-3 protein. ..
  18. Murakami K, Situ S, Eshete F. A gene variation of 14-3-3 zeta isoform in rat hippocampus. Gene. 1996;179:245-9 pubmed
    ..Such mutation in the amino acid sequence is an important indication of the diverse functions of this protein and may also contribute to the recent contradictory observations regarding the role of the 14-3-3 zeta subtype. ..
  19. 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. ..
  20. 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
  21. 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. ..
  22. Laffray S, Bouali Benazzouz R, Papon M, Favereaux A, Jiang Y, Holm T, et al. Impairment of GABAB receptor dimer by endogenous 14-3-3? in chronic pain conditions. EMBO J. 2012;31:3239-51 pubmed publisher
    ..Taken together, our data provide the first example of endogenous regulation of a GPCR oligomeric state and demonstrate its functional impact on the pathophysiological process of neuropathic pain sensitization. ..
  23. Couve A, Kittler J, Uren J, Calver A, Pangalos M, Walsh F, et al. Association of GABA(B) receptors and members of the 14-3-3 family of signaling proteins. Mol Cell Neurosci. 2001;17:317-28 pubmed
    ..The results strongly suggest that GABA(B)R1 and 14-3-3 associate in the nervous system and begin to reveal the signaling complexities of the GABA(B)R1/GABA(B)R2 receptor heterodimer. ..
  24. Watanabe M, Isobe T, Ichimura T, Kuwano R, Takahashi Y, Kondo H, et al. Molecular cloning of rat cDNAs for the zeta and theta subtypes of 14-3-3 protein and differential distributions of their mRNAs in the brain. Brain Res Mol Brain Res. 1994;25:113-21 pubmed
  25. Irwin S, Vandelft M, Pinchev D, Howell J, Graczyk J, Orr H, et al. RNA association and nucleocytoplasmic shuttling by ataxin-1. J Cell Sci. 2005;118:233-42 pubmed
    ..These results suggest that the normal role of ataxin-1 may be in RNA processing, perhaps nuclear RNA export. Thus, nuclear retention of mutant ataxin-1 may be an important toxic gain of function in SCA1 disease. ..
  26. Yuan Z, Agarwal Mawal A, Paudel H. 14-3-3 binds to and mediates phosphorylation of microtubule-associated tau protein by Ser9-phosphorylated glycogen synthase kinase 3beta in the brain. J Biol Chem. 2004;279:26105-14 pubmed
    ..Our data indicate that within the tau phosphorylation complex, 14-3-3 connects Ser(9)-phosphorylated GSK3beta to tau and Ser(9)-phosphorylated GSK3beta phosphorylates tau. ..
  27. Birkenfeld J, Betz H, Roth D. Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3 zeta. Biochem J. 2003;369:45-54 pubmed
    ..Our data are consistent with 14-3-3-protein-induced changes to the actin cytoskeleton resulting from interactions with cofilin and/or LIMK1. ..
  28. Brunet A, Bonni A, Zigmond M, Lin M, Juo P, Hu L, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96:857-68 pubmed
    ..Within the nucleus, FKHRL1 triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene. ..