Genomes and Genes
14 3 3 protein zeta
Gene Symbol: 14 3 3 protein zeta
Description: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta
Alias: 14-3-3-zeta, HEL-S-3, HEL-S-93, HEL4, KCIP-1, YWHAD, 14-3-3 protein zeta/delta, 14-3-3 delta, 14-3-3 protein/cytosolic phospholipase A2, 14-3-3 zeta, epididymis luminal protein 4, epididymis secretory protein Li 3, epididymis secretory protein Li 93, phospholipase A2, protein kinase C inhibitor protein-1, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, delta polypeptide, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, tyrosine 3/tryptophan 5 -monooxygenase activation protein, zeta polypeptide
Products: 14 3 3 protein zeta
- Kostelecky B, Saurin A, Purkiss A, Parker P, McDonald N. Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon. EMBO Rep. 2009;10:983-9 pubmed publisher..This dual-site intra-chain recognition has implications for other 14-3-3 targets, which seem to have only a single 14-3-3 motif, as other lower affinity and cryptic 14-3-3 gatekeeper sites might exist. ..
- Li F, Mofunanya A, Harris K, Takemaru K. Chibby cooperates with 14-3-3 to regulate beta-catenin subcellular distribution and signaling activity. J Cell Biol. 2008;181:1141-54 pubmed publisher..Our results therefore suggest a novel paradigm through which Cby acts in concert with 14-3-3 proteins to facilitate nuclear export of beta-catenin, thereby antagonizing beta-catenin signaling. ..
- Göransson O, Deak M, Wullschleger S, Morrice N, Prescott A, Alessi D. Regulation of the polarity kinases PAR-1/MARK by 14-3-3 interaction and phosphorylation. J Cell Sci. 2006;119:4059-70 pubmed..Collectively, these results indicate that 14-3-3 binding to MARK isoforms is mediated by multiple phosphorylation sites, and serves to anchor MARK isoforms in the cytoplasm. ..
- Chiang C, Kanies C, Kim K, Fang W, Parkhurst C, Xie M, et al. Protein phosphatase 2A dephosphorylation of phosphoserine 112 plays the gatekeeper role for BAD-mediated apoptosis. Mol Cell Biol. 2003;23:6350-62 pubmed..Thus, PP2A dephosphorylation of pSer112 is the key initiating event regulating the activation of BAD during interleukin-3 withdrawal-induced apoptosis. ..
- Li Y, Inoki K, Yeung R, Guan K. Regulation of TSC2 by 14-3-3 binding. J Biol Chem. 2002;277:44593-6 pubmed..Phosphorylation of Ser(1210) in TSC2 is required for its association with 14-3-3. Our data indicate that 14-3-3 association may inhibit the function of TSC2 and represents a possible mechanism of TSC2 regulation. ..
- Cahill C, Tzivion G, Nasrin N, Ogg S, Dore J, Ruvkun G, et al. Phosphatidylinositol 3-kinase signaling inhibits DAF-16 DNA binding and function via 14-3-3-dependent and 14-3-3-independent pathways. J Biol Chem. 2001;276:13402-10 pubmed..Thus, our results demonstrate at least two mechanisms, one 14-3-3-dependent and the other 14-3-3-independent, whereby PI 3-kinase signaling regulates DAF-16 DNA binding and transcription function. ..
- Hashiguchi M, Sobue K, Paudel H. 14-3-3zeta is an effector of tau protein phosphorylation. J Biol Chem. 2000;275:25247-54 pubmed..Our data suggest that 14-3-3zeta is a tau protein effector and may be involved in the abnormal tau phosphorylation occurring during Alzheimer's disease ontogeny. ..
- Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, et al. alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci. 1999;19:5782-91 pubmed..The activity and binding profile of alpha-synuclein suggests that it might act as a protein chaperone and that accumulation of alpha-synuclein could contribute to cell death in neurodegenerative diseases. ..
- Rittinger K, Budman J, Xu J, Volinia S, Cantley L, Smerdon S, et al. Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding. Mol Cell. 1999;4:153-66 pubmed..Structural homology between the 14-3-3 NES structure and those within I kappa B alpha and p53 reveals a conserved topology recognized by the Crm1 nuclear export machinery. ..
- Fanger G, Widmann C, Porter A, Sather S, Johnson G, Vaillancourt R. 14-3-3 proteins interact with specific MEK kinases. J Biol Chem. 1998;273:3476-83 pubmed..With regard to MEKK1, -2 and -3, 14-3-3 proteins do not appear to directly influence activity, but rather function as "scaffolds" for protein-protein interactions. ..
- Wang H, Zhang L, Liddington R, Fu H. Mutations in the hydrophobic surface of an amphipathic groove of 14-3-3zeta disrupt its interaction with Raf-1 kinase. J Biol Chem. 1998;273:16297-304 pubmed..The conservation of the hydrophobic residues Val-176, Leu-216, Leu-220, and Leu-227 among known 14-3-3 family members implies their general importance in ligand binding. ..
- Brummer T, Larance M, Herrera Abreu M, Lyons R, Timpson P, Emmerich C, et al. Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein. EMBO J. 2008;27:2305-16 pubmed..This represents a novel regulatory mechanism with implications for diverse tyrosine kinase signalling systems. ..
- Maxwell S, Li Z, Jaye D, Jaya D, Ballard S, Ferrell J, et al. 14-3-3zeta mediates resistance of diffuse large B cell lymphoma to an anthracycline-based chemotherapeutic regimen. J Biol Chem. 2009;284:22379-89 pubmed publisher..Our study implicates 14-3-3zeta in the pathogenesis of DLBCL and suggests a promising combination strategy with a 14-3-3 inhibitor for the treatment of refractory DLBCL. ..
- Zhang L, Wang H, Liu D, Liddington R, Fu H. Raf-1 kinase and exoenzyme S interact with 14-3-3zeta through a common site involving lysine 49. J Biol Chem. 1997;272:13717-24 pubmed..The parallel effects of this single point mutation on both Raf-1 binding and ExoS activation strongly suggest that diverse associated proteins share a common structural binding determinant on 14-3-3zeta. ..
- LeBron C, Chen L, Gilkes D, Chen J. Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3. EMBO J. 2006;25:1196-206 pubmed..These results suggest that MDMX-14-3-3 interaction plays a role in p53 response to DNA damage by regulating MDMX localization and stability. ..
- Nichols R, Dzamko N, Morrice N, Campbell D, Deak M, Ordureau A, et al. 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization. Biochem J. 2010;430:393-404 pubmed publisher..These results provide the first evidence suggesting that 14-3-3 regulates LRRK2 and that disruption of the interaction of LRRK2 with 14-3-3 may be linked to Parkinson's disease...
- Santoro M, Gaudino G, Marchisio P. The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration. Dev Cell. 2003;5:257-71 pubmed
- Seimiya H, Sawada H, Muramatsu Y, Shimizu M, Ohko K, Yamane K, et al. Involvement of 14-3-3 proteins in nuclear localization of telomerase. EMBO J. 2000;19:2652-61 pubmed..14-3-3 binding was not required for telomerase activity either in vitro or in cell extracts. These observations suggest that 14-3-3 enhances nuclear localization of TERT by inhibiting the CRM1 binding to the TERT NES-like motif. ..
- Muslin A, Tanner J, Allen P, Shaw A. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell. 1996;84:889-97 pubmed..Our findings also suggest novel roles for serine/threonine phosphorylation in the assembly of protein-protein complexes. ..
- Sluchanko N, Chernik I, Seit Nebi A, Pivovarova A, Levitsky D, Gusev N. Effect of mutations mimicking phosphorylation on the structure and properties of human 14-3-3zeta. Arch Biochem Biophys. 2008;477:305-12 pubmed publisher..The triple mutant was highly susceptible to proteolysis. Thus, mutation mimicking phosphorylation of Ser58 destabilized, whereas mutation of Ser184 induced stabilization of 14-3-3zeta structure. ..
- 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. ..
- Freed E, Symons M, Macdonald S, McCormick F, Ruggieri R. Binding of 14-3-3 proteins to the protein kinase Raf and effects on its activation. Science. 1994;265:1713-6 pubmed..Therefore, 14-3-3 proteins may participate in or be required for the regulation of Raf function. These findings suggest a role for 14-3-3 proteins in Raf-mediated signal transduction. ..
- Andersen S, Keijzers G, Rampakakis E, Engels K, Luhn P, El Shemerly M, et al. 14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif. DNA Repair (Amst). 2012;11:267-77 pubmed publisher..Altogether, these results suggest that association may be related to regulation of hEXO1 availability during the DNA damage response to plausibly prevent extensive DNA resection at the damage site, as supported by recent studies. ..
- Ganguly S, Gastel J, Weller J, Schwartz C, Jaffe H, Namboodiri M, et al. Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis. Proc Natl Acad Sci U S A. 2001;98:8083-8 pubmed..Similar switches could play a role in cAMP signal transduction in other biological systems. ..
- Obsil T, Ghirlando R, Klein D, Ganguly S, Dyda F. Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation. Cell. 2001;105:257-67 pubmed
- van der Hoeven P, Van Der Wal J, Ruurs P, Van Dijk M, Van Blitterswijk J. 14-3-3 isotypes facilitate coupling of protein kinase C-zeta to Raf-1: negative regulation by 14-3-3 phosphorylation. Biochem J. 2000;345 Pt 2:297-306 pubmed..We conclude that 14-3-3 facilitates coupling of PKC-zeta to Raf-1 in an isotype-specific and phosphorylation-dependent manner. We suggest that 14-3-3 is a transient mediator of Raf-1 phosphorylation and activation by PKC-zeta. ..
- Li Z, Zhao J, Du Y, Park H, Sun S, Bernal Mizrachi L, et al. Down-regulation of 14-3-3zeta suppresses anchorage-independent growth of lung cancer cells through anoikis activation. Proc Natl Acad Sci U S A. 2008;105:162-7 pubmed..This work not only reveals a critical role of 14-3-3zeta in anoikis suppression in lung cancer cells, but also identifies and validates 14-3-3zeta as a potential molecular target for anticancer therapeutic development. ..
- Yaffe M, Rittinger K, Volinia S, Caron P, Aitken A, Leffers H, et al. The structural basis for 14-3-3:phosphopeptide binding specificity. Cell. 1997;91:961-71 pubmed..Finally, we show that the 14-3-3 dimer binds tightly to single molecules containing tandem repeats of phosphoserine motifs, implicating bidentate association as a signaling mechanism with molecules such as Raf, BAD, and Cbl. ..
- Winter S, Fischle W, Seiser C. Modulation of 14-3-3 interaction with phosphorylated histone H3 by combinatorial modification patterns. Cell Cycle. 2008;7:1336-42 pubmed..Here we discuss the binding of 14-3-3 proteins to histone H3 in detail and putative biological implications of these interactions. ..
- Ku N, Liao J, Omary M. Phosphorylation of human keratin 18 serine 33 regulates binding to 14-3-3 proteins. EMBO J. 1998;17:1892-906 pubmed..Physiological Ser52 or Ser33 phosphorylation on distinct K18 molecules suggests functional compartmentalization of these modifications. ..
- Vincenz C, Dixit V. 14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules. J Biol Chem. 1996;271:20029-34 pubmed..Furthermore, c-Raf and A20 co-immunoprecipitated in a 14-3-3-dependent manner, suggesting that 14-3-3 can function as a bridging or adapter molecule. ..
- Yuan Y, Zhang W, Yan R, Liao Y, Zhao L, Ruan C, et al. Identification of a novel 14-3-3zeta binding site within the cytoplasmic domain of platelet glycoprotein Ibalpha that plays a key role in regulating the von Willebrand factor binding function of glycoprotein Ib-IX. Circ Res. 2009;105:1177-85 pubmed publisher
- Engels K, Giannattasio M, Muzi Falconi M, Lopes M, Ferrari S. 14-3-3 Proteins regulate exonuclease 1-dependent processing of stalled replication forks. PLoS Genet. 2011;7:e1001367 pubmed publisher..We propose that 14-3-3 proteins assist in controlling the phosphorylation status of Exo1 and additional unknown targets, promoting fork progression, stability, and restart in response to DNA replication stress. ..
- Sluchanko N, Sudnitsyna M, Seit Nebi A, Antson A, Gusev N. Properties of the monomeric form of human 14-3-3? protein and its interaction with tau and HspB6. Biochemistry. 2011;50:9797-808 pubmed publisher..Because of minimal changes in structure, MMW and especially WMW mutant proteins are promising candidates for analyzing the effect of monomerization on the physiologically important properties of 14-3-3?. ..
- Fantl W, Muslin A, Kikuchi A, Martin J, MacNicol A, Gross R, et al. Activation of Raf-1 by 14-3-3 proteins. Nature. 1994;371:612-4 pubmed..Expression of 14-3-3 proteins in Xenopus oocytes enhanced Raf-1 activity and promoted Raf-1-dependent oocyte maturation. A dominant negative mutant of Raf-1 blocked the effects of 14-3-3 protein. ..
- Liu D, Bienkowska J, Petosa C, Collier R, Fu H, Liddington R. Crystal structure of the zeta isoform of the 14-3-3 protein. Nature. 1995;376:191-4 pubmed..The residues in the dimer interface and the putative ligand-binding surface are invariant among vertebrates, yeast and plants, suggesting a conservation of structure and function throughout the 14-3-3 family. ..
- Fang D, Hawke D, Zheng Y, Xia Y, Meisenhelder J, Nika H, et al. Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. J Biol Chem. 2007;282:11221-9 pubmed..Phosphorylation of beta-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of beta-catenin plays a critical role in tumor invasion and development. ..
- Thelemann A, Petti F, Griffin G, Iwata K, Hunt T, Settinari T, et al. Phosphotyrosine signaling networks in epidermal growth factor receptor overexpressing squamous carcinoma cells. Mol Cell Proteomics. 2005;4:356-76 pubmed..The functional interactions between IGF-1 receptor, lysophosphatidic acid (LPA) signaling, and EGF receptor were observed, both direct and/or indirectly on phospho-Akt, phospho-Erk1/2, and phospho-ribosomal S6. ..
- Kino T, De Martino M, Charmandari E, Ichijo T, Outas T, Chrousos G. HIV-1 accessory protein Vpr inhibits the effect of insulin on the Foxo subfamily of forkhead transcription factors by interfering with their binding to 14-3-3 proteins: potential clinical implications regarding the insulin resistance of HIV-1-infecte. Diabetes. 2005;54:23-31 pubmed..Vpr thus may contribute to the tissue-selective insulin resistance often observed in HIV-1-infected individuals. ..
- Gannon Murakami L, Murakami K. Selective association of protein kinase C with 14-3-3 zeta in neuronally differentiated PC12 Cells. Stimulatory and inhibitory effect of 14-3-3 zeta in vivo. J Biol Chem. 2002;277:23116-22 pubmed..Our results show that the association with 14-3-3 zeta has distinct effects on classical PKC and non-classical PKC activity. ..
- Gohla A, Bokoch G. 14-3-3 regulates actin dynamics by stabilizing phosphorylated cofilin. Curr Biol. 2002;12:1704-10 pubmed..Taken together, these results suggest that 14-3-3zeta proteins may play a dynamic role in the regulation of cellular actin structures through the maintenance of phosphocofilin levels. ..
- Omi K, Hachiya N, Tanaka M, Tokunaga K, Kaneko K. 14-3-3zeta is indispensable for aggregate formation of polyglutamine-expanded huntingtin protein. Neurosci Lett. 2008;431:45-50 pubmed..This indicates that 14-3-3zeta participates in aggregate formation under nonnative conditions. Our data support a novel role for 14-3-3zeta in the aggregate formation of nonnative, aggregation-prone proteins. ..
- Liu M, Cai S, Espejo A, Bedford M, Walker C. 14-3-3 interacts with the tumor suppressor tuberin at Akt phosphorylation site(s). Cancer Res. 2002;62:6475-80 pubmed..Tuberin also coimmunoprecipitated with 14-3-3, confirming the interaction between endogenous 14-3-3 and tuberin. These data establish the presence of functional and overlapping 14-3-3 and Akt recognition site(s) in tuberin. ..
- 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. ..
- 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. ..
- Tzivion G, Luo Z, Avruch J. Calyculin A-induced vimentin phosphorylation sequesters 14-3-3 and displaces other 14-3-3 partners in vivo. J Biol Chem. 2000;275:29772-8 pubmed..Thus, phosphovimentin, by sequestering 14-3-3 and limiting its availability to other target proteins can affect intracellular signaling processes that require 14-3-3. ..
- Rena G, Prescott A, Guo S, Cohen P, Unterman T. Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targetting. Biochem J. 2001;354:605-12 pubmed
- Ku N, Michie S, Resurreccion E, Broome R, Omary M. Keratin binding to 14-3-3 proteins modulates keratin filaments and hepatocyte mitotic progression. Proc Natl Acad Sci U S A. 2002;99:4373-8 pubmed..Keratin binding to 14-3-3 may partially modulate hepatocyte mitotic progression, in association with nuclear redistribution of 14-3-3 proteins during mitosis. ..
- Powell D, Rane M, Joughin B, Kalmukova R, Hong J, Tidor B, et al. Proteomic identification of 14-3-3zeta as a mitogen-activated protein kinase-activated protein kinase 2 substrate: role in dimer formation and ligand binding. Mol Cell Biol. 2003;23:5376-87 pubmed..These data suggest that MAPKAPK2-mediated phosphorylation regulates 14-3-3zeta functions, and this MAPKAPK2 activity may represent a novel pathway mediating p38 MAPK-dependent inflammation. ..
- Sluchanko N, Sudnitsyna M, Chernik I, Seit Nebi A, Gusev N. Phosphomimicking mutations of human 14-3-3? affect its interaction with tau protein and small heat shock protein HspB6. Arch Biochem Biophys. 2011;506:24-34 pubmed publisher..Thus, effect of 14-3-3 phosphorylation depends on the nature of the target protein and therefore, phosphorylation of 14-3-3 might affect its target specificity. ..
- Oksvold M, Huitfeldt H, Langdon W. Identification of 14-3-3zeta as an EGF receptor interacting protein. FEBS Lett. 2004;569:207-10 pubmed..Our finding adds to the growing complexity of EGF receptor signaling and indicates a role for 14-3-3 proteins in EGF receptor signaling or regulation. ..
- Soulie C, Nicole A, Delacourte A, Ceballos Picot I. Examination of stress-related genes in human temporal versus occipital cortex in the course of neurodegeneration: involvement of 14-3-3 zeta in this dynamic process. Neurosci Lett. 2004;365:1-5 pubmed..This data obtained directly from human brains confirmed a 14-3-3 zeta implication in the Alzheimer's neuropathology. ..
- Tian Q, Feetham M, Tao W, He X, Li L, Aebersold R, et al. Proteomic analysis identifies that 14-3-3zeta interacts with beta-catenin and facilitates its activation by Akt. Proc Natl Acad Sci U S A. 2004;101:15370-5 pubmed..We propose that Akt phosphorylates beta-catenin, which results in 14-3-3zeta binding and stabilization of beta-catenin, and these interactions may be involved in stem cell development. ..
- MacDonald N, Welburn J, Noble M, Nguyen A, Yaffe M, Clynes D, et al. Molecular basis for the recognition of phosphorylated and phosphoacetylated histone h3 by 14-3-3. Mol Cell. 2005;20:199-211 pubmed..14-3-3 isoforms thus represent a class of proteins that mediate the effect of histone phosphorylation at inducible genes. ..
- Niemantsverdriet M, Wagner K, Visser M, Backendorf C. Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character. Oncogene. 2008;27:1315-9 pubmed
- Matta A, Bahadur S, Duggal R, Gupta S, Ralhan R. Over-expression of 14-3-3zeta is an early event in oral cancer. BMC Cancer. 2007;7:169 pubmed..Thus, 14-3-3zeta may serve as an important molecular target for designing novel therapy for oral cancer. ..