Affinage

YWHAZ

14-3-3 protein zeta/delta · UniProt P63104

Round 2 corrected
Length
245 aa
Mass
27.7 kDa
Annotated
2026-04-28
130 papers in source corpus 42 papers cited in narrative 42 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YWHAZ (14-3-3ζ) is a dimeric phosphoserine/phosphothreonine-binding scaffold protein that engages a broad repertoire of signaling clients through its conserved amphipathic groove, functioning as a central integrator of Ras-MAPK, PI3K-Akt-mTOR, Wnt/β-catenin, TGF-β/Smad, and apoptotic signaling pathways (PMID:8601312, PMID:9428519, PMID:18439900, PMID:17287208). By sequestering phosphorylated partners—including FKHRL1/FoxO, BAD, Cdc25C, raptor, β-catenin, Smad3, and the androgen receptor—in specific subcellular compartments, YWHAZ controls their stability, localization, and transcriptional or enzymatic activity, thereby modulating cell survival, proliferation, EMT, and cytoskeletal remodeling (PMID:10102273, PMID:22912335, PMID:12810725, PMID:34697370). YWHAZ additionally participates in innate immune signaling by promoting TICAM-1 multimerization downstream of TLR3, regulates intestinal GLP-1 secretion and islet paracrine cross-talk, and its mRNA stability is controlled by the m6A/YBX1/IGF2BP axis (PMID:27058640, PMID:27167773, PMID:36512307). A gain-of-function YWHAZ variant (S230W) hyperactivates RAF-ERK signaling and is associated with cardio-facio-cutaneous (CFC) syndrome (PMID:31024343).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1992 High

    Establishing the biochemical identity of 14-3-3ζ as an alpha-helical PKC inhibitor resolved how this abundant brain protein interfaces with kinase cascades, though its broader signaling role was unknown.

    Evidence Purification from sheep brain, direct sequencing, in vitro kinase assays with multiple kinases

    PMID:1317796

    Open questions at the time
    • Mechanism of PKC inhibition unclear (does not inhibit catalytic fragment PKM)
    • In vivo relevance not established
    • Whether PKC regulation is the primary function was unknown
  2. 1996 High

    Demonstrating that 14-3-3ζ recognizes phosphoserine motifs on client proteins and that phosphopeptides disrupt these complexes established the fundamental molecular recognition principle governing 14-3-3 interactions.

    Evidence Phosphopeptide binding assays, co-IP disruption, Xenopus oocyte maturation assay

    PMID:8601312

    Open questions at the time
    • Structural basis of phosphoserine recognition not yet resolved
    • Breadth of client repertoire unknown
  3. 1997 High

    Crystal structure determination of 14-3-3ζ bound to a phosphoserine peptide, combined with identification of two consensus binding motifs (RSXpSXP and RXY/FXpSXP) and the bidentate binding mode, provided the structural framework for understanding how the amphipathic groove engages diverse clients.

    Evidence X-ray crystallography at 2.6 Å, phosphoserine-oriented peptide library, ITC

    PMID:9428519

    Open questions at the time
    • How groove residues are differentially used for distinct clients was unclear
    • Whether phosphorylation-independent interactions also use the groove
  4. 1997 High

    Mapping the 14-3-3ζ interaction to the Raf-1 cysteine-rich domain and showing that disrupting this contact hyperactivates Raf-1 transforming activity defined 14-3-3ζ as a negative regulator of Raf, complemented by Drosophila genetic epistasis placing 14-3-3ζ between Ras and Raf in vivo.

    Evidence Direct binding with isolated CRD, mutagenesis/transformation assays; Drosophila genetic epistasis with Ras/Raf alleles

    PMID:9159395 PMID:9261098

    Open questions at the time
    • How 14-3-3ζ toggles between positive and negative Raf regulation not resolved
    • Role of dimerization in Raf regulation unknown
  5. 1999 High

    Site-directed mutagenesis of groove residues showed that basic residues are critical for ExoS activation whereas hydrophobic residues matter for Raf-1 binding, establishing that the amphipathic groove employs distinct sub-surfaces for different clients.

    Evidence Mutagenesis of 14-3-3ζ groove, in vitro ExoS ADP-ribosyltransferase activity assay

    PMID:10508420

    Open questions at the time
    • Limited to two clients (ExoS and Raf-1); generalizability to other partners untested
  6. 1999 High

    Showing that Akt-phosphorylated FKHRL1 is sequestered in the cytoplasm by 14-3-3 binding established a paradigm in which 14-3-3ζ acts as a phosphorylation-dependent cytoplasmic anchor controlling transcription factor nuclear access and apoptotic gene programs.

    Evidence Co-IP, subcellular fractionation, dominant-negative Akt, reporter assays

    PMID:10102273

    Open questions at the time
    • Whether all FoxO family members use the same mechanism not shown
    • Kinetics of release upon survival factor withdrawal uncharacterized
  7. 2003 High

    Interaction with cofilin, LIMK1, and integrin-induced Cdc42/Rac1 activation linked 14-3-3ζ to actin cytoskeletal dynamics and cell spreading, extending its role beyond kinase cascades to Rho GTPase signaling downstream of integrins.

    Evidence Y2H, GST pull-down, actin co-sedimentation, Rho GTPase assays, GP Ibα sequestration and rescue experiments in CHO cells

    PMID:12323073 PMID:12810725

    Open questions at the time
    • Precise activation mechanism linking 14-3-3ζ to GEFs for Cdc42/Rac1 unidentified
    • In vivo relevance in primary cells not established
  8. 2004 High

    FRAP-based quantification of nuclear-cytoplasmic shuttling showed that differential Crm1-dependent export rates underlie isoform-specific subcellular distribution between 14-3-3ζ (more nuclear) and 14-3-3σ, resolving how identical groove chemistry can yield distinct functional outputs by localization.

    Evidence YFP fusion FRAP, leptomycin B treatment, isoform-specific immunostaining

    PMID:14996909

    Open questions at the time
    • Structural determinants of differential export rates not mapped
    • Functional consequence of nuclear 14-3-3ζ pool uncharacterized
  9. 2007 High

    AKT-mediated phosphorylation of β-catenin at Ser552 was shown to promote 14-3-3ζ binding, protecting β-catenin from β-TrCP ubiquitination, stabilizing its cytosolic/nuclear pool and enhancing Wnt target transcription and tumor invasion, establishing a direct mechanism for 14-3-3ζ in Wnt/β-catenin pathway activation.

    Evidence In vitro kinase assay, phospho-specific antibodies, co-IP, ubiquitination assay, invasion assay, in vivo metastasis model

    PMID:17287208 PMID:22912335

    Open questions at the time
    • Whether other 14-3-3 isoforms provide redundant β-catenin stabilization unknown
    • Tissue-specificity of this axis unclear
  10. 2008 High

    Demonstrating that AMPK-phosphorylated raptor recruits 14-3-3 to suppress mTORC1 under energy stress positioned 14-3-3ζ at the nexus of metabolic sensing, connecting the energy-sensing AMPK to the growth-promoting mTOR pathway.

    Evidence In vitro AMPK kinase assay, phospho-site mutagenesis, co-IP of 14-3-3/raptor, cell-cycle analysis

    PMID:18439900

    Open questions at the time
    • Isoform specificity of 14-3-3 binding to raptor not resolved
    • Stoichiometry and dynamics of complex formation in vivo unknown
  11. 2008 High

    14-3-3ζ overexpression was shown to suppress p53 via the PI3K/Akt/MDM2 axis and sequester BAD to protect against anoikis and anoxia-reoxygenation injury, consolidating its anti-apoptotic function across multiple stress contexts.

    Evidence 3D Matrigel culture, transgenic mouse MECs, p53 rescue; siRNA double KD with BAD fractionation and anoxia-reoxygenation injury assay

    PMID:18339856 PMID:18640115

    Open questions at the time
    • Relative contribution of MDM2 axis vs. BAD sequestration in different tissue types unclear
  12. 2013 High

    Crystal structures of 14-3-3ζ bound to integrin β4 tail peptides, combined with NMR and SPR for other β-integrin tails, revealed both canonical phosphopeptide-binding and novel phosphorylation-independent interaction modes, expanding the repertoire of 14-3-3ζ client recognition.

    Evidence X-ray crystallography, NMR, SPR, ITC, mutagenesis

    PMID:23763993

    Open questions at the time
    • Functional consequence of 14-3-3ζ/integrin tail binding on integrin signaling not fully delineated
  13. 2016 Medium

    Ywhaz knockout mice revealed physiological roles beyond cancer: negative regulation of intestinal GLP-1 secretion and actomyosin contraction via RhoA, and promotion of TLR3 innate immune signaling via TICAM-1 multimerization, demonstrating tissue-specific in vivo functions.

    Evidence Whole-body Ywhaz KO mouse with GLP-1R antagonist rescue; siRNA in TM cells with phospho-MLC/RhoA readouts; siRNA with TICAM-1 multimerization assay

    PMID:26906158 PMID:27058640 PMID:27167773

    Open questions at the time
    • Downstream effectors linking 14-3-3ζ to GLP-1 production unidentified
    • Whether actomyosin effects are direct or through regulation of RhoA stability remains unclear
  14. 2019 Medium

    A gain-of-function YWHAZ variant (S230W) that escapes CK1α phosphorylation and hyperactivates RAF-ERK signaling was linked to CFC syndrome, providing the first evidence that YWHAZ mutations cause a human developmental RASopathy.

    Evidence Xenopus ectopic expression, embryo phenotyping, co-IP with Raf, ERK phosphorylation assay, CK1α phosphorylation assay

    PMID:31024343

    Open questions at the time
    • Human genetic validation limited; awaits identification in larger CFC cohorts
    • Structural basis for S230W gain-of-function not determined
  15. 2021 High

    PIM1 was shown to phosphorylate 14-3-3ζ and coordinate its interaction with the androgen receptor for co-occupancy of chromatin sites, establishing 14-3-3ζ as a transcriptional co-regulator on chromatin, not merely a cytoplasmic scaffold.

    Evidence In vitro PIM1 kinase assay, RIME, ChIP-seq, gene expression analysis in prostate cancer cells

    PMID:34697370

    Open questions at the time
    • Genome-wide binding sites not validated across cell types
    • Whether chromatin occupancy is limited to AR-driven contexts unknown
  16. 2022 Medium

    YBX1/IGF2BP-dependent m6A modification was shown to control YWHAZ mRNA stability, and zebrafish ywhaz KO revealed monoaminergic neurotransmission defects, expanding understanding of YWHAZ regulation and neuronal function.

    Evidence RIP, RNA decay assay, CRISPR KO zebrafish, whole-brain imaging, monoamine HPLC, pharmacological rescue

    PMID:35501409 PMID:36512307

    Open questions at the time
    • Specific m6A sites on YWHAZ mRNA not mapped
    • Whether monoamine defects reflect developmental or acute synaptic roles of 14-3-3ζ unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for isoform-specific client selectivity among 14-3-3 family members, the full scope of phosphorylation-independent interactions, and how nuclear 14-3-3ζ functions as a transcriptional co-regulator across different chromatin contexts.
  • No systematic comparison of all seven human 14-3-3 isoform client preferences exists
  • Comprehensive structural catalog of phosphorylation-independent binding modes is lacking
  • In vivo phenotyping of conditional tissue-specific Ywhaz knockouts remains incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 8 GO:0098772 molecular function regulator activity 5
Localization
GO:0005829 cytosol 4 GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 1
Partners
ARCTNNB1DAAM1FOXO3RAF1RPTORTMEM65TRIM21
Complex memberships
14-3-3 homodimer/heterodimerGP Ib-IX-V/14-3-3ζ complexmTORC1 (via raptor/14-3-3 association)

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 YWHAZ (14-3-3ζ, KCIP-1) is a potent inhibitor of protein kinase C (PKC) isolated from sheep brain; it consists of multiple isoforms with acetylated N-termini, adopts a predominantly alpha-helical amphipathic structure, and four isoforms serve as PKC substrates in vitro (phosphorylated by PKC itself), but it does not inhibit the isolated catalytic fragment of PKC (PKM) nor cAMP-dependent kinase, CaM kinase II, or casein kinase 2. Reverse-phase HPLC isoform separation, direct protein sequencing, in vitro kinase assays, secondary structure prediction European journal of biochemistry High 1317796
1996 14-3-3ζ binds signaling proteins through specific recognition of phosphoserine-containing motifs; phosphoserine is necessary and sufficient for binding, and phosphopeptides based on the Raf-1 binding motif can disrupt 14-3-3 complexes and inhibit Xenopus oocyte maturation. Phosphopeptide binding assays, co-immunoprecipitation disruption, Xenopus oocyte maturation assay Cell High 8601312
1995 14-3-3ζ self-assembles into dimers via its amino-terminal sequences, while Raf-1 binding requires the carboxy-terminal ~100 amino acids; 14-3-3ζ acts as an arachidonate-selective acyltransferase/putative phospholipase A2; it binds both active and inactive Raf in situ, and truncated forms that bind Raf are only recovered with inactive Raf, indicating 14-3-3ζ participates in the Raf activation process. Baculoviral recombinant protein binding, yeast two-hybrid, deletion analysis, co-purification from Sf9 cells, COS cell co-expression The Journal of biological chemistry High 7559537
1997 The crystal structure of 14-3-3ζ complexed with a phosphoserine motif from polyoma middle-T antigen (2.6 Å resolution) reveals an extended peptide conformation with a tight turn at the pS+2 Pro residue; two consensus binding motifs (RSXpSXP and RXY/FXpSXP) were identified using phosphoserine-oriented peptide libraries; the 14-3-3ζ dimer binds tightly to molecules containing tandem phosphoserine motifs via bidentate association. X-ray crystallography (2.6 Å), phosphoserine-oriented peptide library screening, ITC binding measurements Cell High 9428519
1997 14-3-3ζ binds directly to the Raf-1 cysteine-rich domain (CRD, residues 139–184); mutation of Raf-1 residues 143–145 impairs 14-3-3ζ binding but not Ras binding to the CRD; introduction of these mutations produces full-length Raf-1 mutants with enhanced transforming activity, demonstrating that 14-3-3ζ interaction with the Raf-CRD negatively regulates Raf-1 function. Direct binding assays with isolated CRD, site-directed mutagenesis, transformation assays The Journal of biological chemistry High 9261098
1997 In Drosophila, 14-3-3ζ (D14-3-3ζ) is an essential component of the Ras/Raf/MAPK signaling pathway required for photoreceptor differentiation; it acts upstream of Raf and downstream of Ras, as shown by genetic epistasis with gain-of-function Raf and Ras alleles; it localizes apically in differentiating photoreceptor cells. Drosophila genetic epistasis (mutant analysis + gain-of-function rescue), in situ hybridization, immunolocalization Genes & development High 9159395
1997 14-3-3ζ binds to the carboxyl half of mouse Wee1 kinase; this interaction occurs in vitro and in COS-1 cells (co-immunoprecipitation); the Wee1 kinase phosphorylated by Cdc2 also binds 14-3-3ζ; both the kinase domain and a C-terminal sequence of Wee1 are required for binding. Yeast two-hybrid, in vitro binding with recombinant proteins, co-immunoprecipitation in COS-1 cells, deletion analysis Biochemical and biophysical research communications Medium 9016762
1998 14-3-3ζ binds to discrete amino acid sequences within the cytoplasmic domain of the platelet glycoprotein Ib-IX-V complex: the C-terminal GHSL sequence of GPIbα, the central GPIbα region (Arg557–Gly575), and sequences in GPIbβ and GPV; phosphorylation of GPIbβ at Ser166 (a PKA site) enhances 14-3-3ζ binding ~8-fold, suggesting phosphorylation-regulated association. Peptide binding assay with radiolabeled 14-3-3ζ, alanine-walking mutagenesis, immunoprecipitation from platelet extracts, peptide competition Biochemistry High 9425086
1995 14-3-3ζ differentially activates PKC isoforms: classical PKC isoforms are activated ~2-fold, PKCδ shows no significant activation, and PKCε is highly activated with strong positive cooperativity (Hill coefficient ~6.1), indicating isoform-specific regulation of PKC by 14-3-3ζ. In vitro PKC activity assay with purified 14-3-3ζ and purified PKC isoforms Biochemical and biophysical research communications Medium 7488074
1999 The conserved basic residues lining the amphipathic groove of 14-3-3ζ are required for activation of Pseudomonas aeruginosa ExoS ADP-ribosyltransferase, whereas hydrophobic residues of the groove are less critical; Val176 (required for Raf-1 interaction) is dispensable for ExoS binding and activation, demonstrating selective use of groove residues for different client proteins. Site-directed mutagenesis of 14-3-3ζ groove residues, in vitro ExoS ADP-ribosyltransferase activity assay, binding assays Biochemistry High 10508420
1999 Akt phosphorylates the Forkhead transcription factor FKHRL1, leading to its association with 14-3-3 proteins (including 14-3-3ζ) and cytoplasmic retention; survival factor withdrawal leads to dephosphorylation, nuclear translocation, and target gene (e.g., Fas ligand) activation, establishing 14-3-3ζ as a cytoplasmic anchor that sequesters phospho-FKHRL1 downstream of Akt. Co-immunoprecipitation, subcellular fractionation, reporter gene assays, dominant-negative Akt, phospho-specific antibodies Cell High 10102273
2003 14-3-3ζ interacts with cofilin and LIMK1 via consensus 14-3-3 binding sites identified by deletion analysis; 14-3-3ζ co-sedimentation experiments show its C-terminal region inhibits cofilin binding to actin; upon co-transfection, 14-3-3ζ redistributes into LIMK1-induced actin aggregations, linking 14-3-3ζ to actin cytoskeletal reorganization. Yeast two-hybrid, GST pull-down, deletion analysis, co-sedimentation with actin, co-transfection and immunofluorescence in COS-7 cells The Biochemical journal High 12323073
2003 14-3-3ζ mediates integrin-induced activation of Cdc42 and Rac1 in CHO cells; GP Ibα expression sequesters 14-3-3ζ via its cytoplasmic domain, blocking integrin-induced Rho GTPase activation and cell spreading; re-expression of 14-3-3ζ restores these responses, identifying 14-3-3ζ as a mediator of integrin-to-Rho GTPase signaling. CHO cell expression of GP Ibα constructs, Rho GTPase activation assays, cytoskeletal staining, cell spreading assay, rescue by 14-3-3ζ overexpression The Journal of biological chemistry High 12810725
2003 Three subclasses of PKC (classical, novel, atypical) all interact with 14-3-3ζ in the rodent brain; the PKC/14-3-3ζ complex pool (1–4% of each PKC isoform) displays constitutive, autonomous, Ca2+-independent kinase activity; C1 domain of PKC is involved in 14-3-3ζ binding, and the interaction is at least partially phosphorylation-independent. Co-immunoprecipitation from rodent brain, PKC activity assay of immunoprecipitate, Western blotting Journal of neurochemistry Medium 12485398
2004 14-3-3ζ has a higher nuclear fraction than 14-3-3σ in mammalian cells; FRAP experiments demonstrate both isoforms rapidly shuttle between nucleus and cytoplasm via active transport; 14-3-3σ has a 1.7× higher nuclear export rate constant (Crm1/leptomycin B-sensitive), establishing that isoform-specific subcellular distribution arises from differential nuclear export kinetics. YFP fusion live-cell imaging, isoform-specific antibody immunostaining, FRAP, leptomycin B treatment Journal of cell science High 14996909
2005 AMPK phosphorylates raptor on two conserved serine residues, inducing 14-3-3 binding to raptor; this 14-3-3 association is required for energy stress-induced mTORC1 inhibition and cell-cycle arrest, placing 14-3-3ζ as a mediator of AMPK-dependent mTORC1 pathway suppression. In vitro AMPK kinase assay, phospho-site mutagenesis, co-immunoprecipitation of 14-3-3/raptor, cell-cycle analysis under energy stress Molecular cell High 18439900
2005 ERK-mediated hyperphosphorylation of Raf-1 at six feedback sites (five proline-directed ERK sites) desensitizes Raf-1; re-sensitization requires PP2A dephosphorylation and Pin1 prolyl isomerase; 14-3-3 interaction with Raf-1 is modulated by this feedback phosphorylation cycle, contributing to precise temporal control of Ras signaling. Phospho-site mapping by MS, site-directed mutagenesis, PP2A and Pin1 interaction assays, Raf-1 kinase activity measurements Molecular cell High 15664191
2007 AKT phosphorylates β-catenin at Ser552, causing its dissociation from cell-cell contacts and accumulation in cytosol/nucleus; phospho-Ser552 β-catenin interacts with 14-3-3ζ via a binding motif containing Ser552, enhancing β-catenin transcriptional activity and tumor cell invasion. In vitro kinase assay, phospho-specific antibodies, co-immunoprecipitation, invasion assay, mutagenesis of Ser552 The Journal of biological chemistry High 17287208
2007 14-3-3ζ knockdown in mammalian cells sensitizes cells to stress-induced apoptosis and activates JNK/p38 signaling; it also enforces cell-cell contacts and upregulates adhesion proteins, demonstrating isoform-specific oncogenic activities: restraining apoptosis propensity and cell adhesion. siRNA knockdown, apoptosis assays, JNK/p38 signaling readout, cell adhesion assays, Oncomine meta-analysis Oncogene Medium 17704798
2008 14-3-3ζ overexpression in MCF10A cells activates the PI3K/Akt pathway leading to MDM2 phosphorylation and nuclear translocation, which increases p53 degradation and resistance to anoikis; ectopic p53 expression restores luminal apoptosis, placing 14-3-3ζ upstream of the Akt/MDM2/p53 axis in mammary epithelial architecture. 3D Matrigel culture, transgenic mouse MECs, siRNA/overexpression, Western blot for phospho-MDM2/p53 levels, anoikis assays, p53 rescue Cancer research High 18339856
2008 SIRT2 negatively regulates 14-3-3ζ levels; SIRT2 knockdown induces 14-3-3ζ expression, which facilitates cytosolic sequestration of BAD (reducing mitochondrial BAD), thereby protecting H9c2 cells from anoxia-reoxygenation injury; concurrent knockdown of both SIRT2 and 14-3-3ζ abolishes the cytoprotective phenotype. siRNA double knockdown, gene array, subcellular fractionation of BAD, anoxia-reoxygenation injury assay FEBS letters Medium 18640115
2008 Depletion of 14-3-3ζ in mouse hippocampal cultures induces ER stress markers (KDEL-containing proteins, calnexin upregulation) and granule cell death; 14-3-3ζ levels increase in the microsomal/ER-containing fraction upon ER stress (tunicamycin) or excitotoxicity (kainic acid); 14-3-3ζ knockdown exacerbates kainic acid-induced damage in all hippocampal subfields. siRNA knockdown in organotypic cultures, subcellular fractionation, Western blot for ER stress markers, kainic acid injury assay Journal of neurochemistry Medium 18466333
2010 14-3-3ζ overexpression negatively modulates TGF-β1-mediated growth inhibition; it increases linker-phosphorylated Smad3 (which cannot mediate growth arrest); mutation of 14-3-3ζ phosphorylation sites on Smad3 rescues TGF-β1-induced p15 promoter activity and cell-cycle arrest, identifying Smad3 as a critical functional target of 14-3-3ζ in TGF-β resistance. siRNA/overexpression, Smad3 phosphorylation site mutagenesis, p15 promoter-reporter assay, cell-cycle analysis Molecules and cells Medium 20082218
2011 miR-451 suppresses Ywhaz expression through its 3'UTR and this suppression mediates downregulation of p38 MAPK signaling; miR-451 overexpression inhibits glomerular mesangial cell proliferation in vitro and in vivo through this Ywhaz/p38 MAPK axis. Luciferase 3'UTR reporter assay, Western blot, in vitro proliferation assay, in vivo mesangial cell model FEBS letters Medium 21827757
2011 Fusicoccin-based fluorescent probes form ternary complexes with 14-3-3ζ and phosphopeptide ligands and site-specifically attach a fluorescent tag onto the surface of 14-3-3ζ proteins in a phosphopeptide-dependent manner, revealing the ligand-binding interface. Chemical biology/affinity labeling with cell-penetrating diterpene probes, fluorescence readout Angewandte Chemie (International ed. in English) Medium 22105970
2011 Lacosamide (an antiepileptic drug) binds to 14-3-3ζ in rodent brain lysates in a stereospecific, xanthine-dependent manner; the adduction site was mapped to K120 by MS; competition experiments confirm (R)-lacosamide and the affinity probe share the same binding site on 14-3-3ζ; xanthine interaction with 14-3-3ζ was confirmed by isothermal calorimetry. Affinity bait/chemical reporter strategy, LC-MS/MS adduction site mapping, competition binding, isothermal calorimetry Journal of the American Chemical Society Medium 21692503
2012 YWHAZ promotes epithelial-mesenchymal transition (EMT) and lung cancer metastasis through interaction with β-catenin: YWHAZ binds β-catenin, protects it from β-TrCP-mediated ubiquitination and proteasomal degradation, and promotes its cytosolic/nuclear accumulation and transcriptional activity; S552-phosphorylated β-catenin shows enhanced YWHAZ complex formation; knockdown reverses EMT. Co-immunoprecipitation, ubiquitination assay, dominant-negative/positive β-catenin mutants, shRNA knockdown, in vivo metastasis model Molecular cancer research : MCR High 22912335
2013 14-3-3ζ interacts with the cytoplasmic tails of α4, β1, β2, and β3 integrin subunits; X-ray crystallography of the 14-3-3ζ/α4 complex (canonical phosphopeptide-binding mode) reveals residues outside the consensus motif are essential for efficient interaction; a short β2 phospho-peptide alone is sufficient for high-affinity binding; the β1A integrin tail shows the strongest interaction; novel phosphorylation-independent interactions are also identified. X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mutagenesis Journal of molecular biology High 23763993
2014 YWHAZ transcription is regulated by a functional CRE element in the proximal promoter of the predominant transcript variant (1c); ATF-1 (and, to a lesser extent, CREB) bind the endogenous YWHAZ promoter especially under TNF-α stimulation; ATF-1 silencing markedly reduces two of five YWHAZ transcript variants. 5'RACE, EMSA, chromatin immunoprecipitation (ChIP), promoter-reporter assay, ATF-1 siRNA, EST database mining PloS one Medium 24690670
2014 14-3-3ζ depletion in glioblastoma cells induces cellular senescence through p27 accumulation caused by impaired SKP2-mediated ubiquitin degradation of p27; the mechanism involves loss of STAT3 solubility (increased insoluble STAT3 fraction); ectopic 14-3-3ζ blocks BIS-depletion-induced senescence with parallel decrease in insoluble STAT3, placing 14-3-3ζ in the BIS/14-3-3ζ/STAT3/SKP2/p27 senescence pathway. siRNA/shRNA knockdown, senescence assays (SA-β-gal), Western blot of soluble/insoluble fractions, ectopic overexpression rescue, Bis-KO mouse embryonic fibroblasts Cell death & disease Medium 25412315
2016 14-3-3ζ participates in TLR3-mediated signaling by promoting TICAM-1 multimerization: 14-3-3ζ knockdown reduces type I interferon and inflammatory cytokine production, blocks IRF3 nuclear translocation, and inhibits TICAM-1 multimer formation after TLR3 ligand stimulation. siRNA knockdown, TICAM-1 multimerization assay (native gel), IRF3 nuclear translocation assay, cytokine ELISA, IκB phosphorylation Molecular immunology Medium 27058640
2016 14-3-3ζ downregulation in trabecular meshwork (TM) cells decreases MLC and cofilin phosphorylation, reduces stress fiber and focal adhesion formation, alters ECM composition (fibronectin/collagen mRNA), and inhibits TGF-β1-induced cell contraction; this is mediated through direct reduction of total RhoA levels, placing 14-3-3ζ upstream of RhoA in actomyosin regulation. siRNA knockdown, Western blot (phospho-MLC, phospho-cofilin, RhoA), immunofluorescence, collagen gel contraction assay, qRT-PCR Investigative ophthalmology & visual science Medium 26906158
2016 Ywhaz knockout mice display elevated fasting GLP-1 levels and improved oral glucose tolerance; 14-3-3ζ knockdown in GLUTag L cells elevates GLP-1 synthesis and release; systemic GLP-1 receptor inhibition abolishes the improved oral glucose tolerance of knockout mice, demonstrating that 14-3-3ζ negatively regulates GLP-1 production in intestinal L cells. Whole-body Ywhaz KO mouse, oral vs. IP glucose tolerance test, GLP-1 ELISA, siRNA in GLUTag cells, GLP-1R antagonist rescue Endocrinology High 27167773
2019 A gain-of-function YWHAZ variant (S230W) associated with CFC syndrome activates the RAF-ERK pathway: it binds more Raf protein than wild-type YWHAZ, enhances Raf-stimulated ERK phosphorylation, induces severe embryonic defects in Xenopus more efficiently than wild type, rescues dominant-negative FGF receptor defects more potently, and escapes phosphorylation by casein kinase 1a. Xenopus laevis ectopic expression, embryo phenotype scoring, dominant-negative FGF receptor rescue assay, co-immunoprecipitation of Raf, ERK phosphorylation Western blot, casein kinase 1a phosphorylation assay Frontiers in physiology Medium 31024343
2020 PPD (20(S)-protopanaxadiol, a ginsenoside metabolite) directly binds to 14-3-3ζ; co-crystal structure reveals main interactions at R56, R127, and Y128 of 14-3-3ζ; mutagenesis of any of these residues significantly decreases PPD affinity, identifying a dammarane-type triterpenoid binding site on the protein surface. Affinity chromatography, biolayer interferometry (BLI), isothermal titration calorimetry (ITC), X-ray co-crystallography, site-directed mutagenesis Journal of ginseng research High 34295206
2021 YWHAZ interacts with and colocalizes with DAAM1 in breast cancer cells; this YWHAZ-DAAM1 complex is essential for DAAM1-mediated microfilament remodeling and RhoA activation; miR-613 directly targets both YWHAZ and DAAM1, inhibiting breast cancer cell migration by disrupting the YWHAZ-DAAM1 complex. Co-immunoprecipitation, co-localization (immunofluorescence), RhoA activation assay, miR-613 mimic transfection, migration assay Cell death discovery Medium 34453038
2021 PIM1 phosphorylates 14-3-3ζ as an endogenous substrate in prostate cancer cells; PIM1 phosphorylation of both the androgen receptor (AR) at S213 and 14-3-3ζ coordinates their interaction; the AR/14-3-3ζ complex extensively co-occupies chromatin sites and recruits co-regulators (hnRNPK, TRIM28) to drive PIM1-dependent transcription of cell migration/invasion genes. In vitro PIM1 kinase assay, co-immunoprecipitation, ChIP-seq/ChIP, RIME (rapid immunoprecipitation and MS of endogenous proteins), gene expression analysis Communications biology High 34697370
2021 TRIM21 E3 ligase interacts with YWHAZ (identified by Co-IP/LC-MS/MS and validated by BIFC); TRIM21 negatively regulates YWHAZ protein levels via its RING domain (E3 ligase activity), promoting ubiquitin-mediated degradation of YWHAZ. Co-immunoprecipitation coupled with LC-MS/MS, bimolecular fluorescence complementation (BIFC), TRIM21-ΔRING mutant, Western blot Biomedical and environmental sciences : BES Medium 29673441
2022 ywhaz deficiency in zebrafish alters neuronal activity and connectivity in the hindbrain; adult ywhaz KO fish have decreased monoamine levels in the hindbrain and display a freezing phenotype to novel stimuli that is reversed by drugs targeting monoamine neurotransmission, establishing a role for ywhaz in establishing neuronal connectivity and modulating monoaminergic neurotransmission. CRISPR/Cas9 KO zebrafish, whole-brain light-sheet imaging, monoamine HPLC measurements, behavioral assays, pharmacological rescue Molecular psychiatry Medium 35501409
2022 YBX1 cooperates with the m6A reader IGF2BPs to stabilize YWHAZ mRNA in an m6A-dependent manner; YBX1 deletion decreases YWHAZ expression by accelerating mRNA decay; restoration of YWHAZ rescues proliferation and survival defects of YBX1-deficient CML leukemia stem cells, positioning YWHAZ downstream of YBX1/m6A in LSC maintenance. RNA decay assay, RNA immunoprecipitation (RIP), co-immunoprecipitation (YBX1/IGF2BPs), RNA sequencing, flow cytometry, rescue overexpression Cellular oncology Medium 36512307
2022 14-3-3ζ mediates the effect of β-cell GLP-1R agonist signaling on α cell proglucagon processing; a secreted protein factor regulated by 14-3-3ζ in islets mediates paracrine cross-talk; α cell ablation blunts liraglutide-enhanced GSIS, and 14-3-3ζ in α cells regulates GLP-1 production from proglucagon. α-cell ablation mouse model, 14-3-3ζ knockdown in islets, GLP-1 secretion assay, liraglutide treatment, GLP-1R antagonist Science advances Medium 35867787
2024 TMEM65 directly binds YWHAZ in the cytoplasm and inhibits ubiquitin-mediated degradation of YWHAZ; TMEM65 exerts oncogenic effects through activation of the PI3K-Akt-mTOR pathway via YWHAZ; TMEM65 oncogenic activity is partly dependent on YWHAZ as shown by rescue experiments. Co-immunoprecipitation, Western blot (ubiquitination), siRNA rescue, PI3K-Akt-mTOR pathway phosphorylation analysis, xenograft model Oncogene Medium 38341472

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 5502 10102273
2008 AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular cell 3139 18439900
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1997 The structural basis for 14-3-3:phosphopeptide binding specificity. Cell 1405 9428519
1996 Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell 1220 8601312
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2012 The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Science signaling 1110 22692423
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2007 Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nature cell biology 949 17277771
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2007 Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. The Journal of biological chemistry 748 17287208
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
1995 FAP-1: a protein tyrosine phosphatase that associates with Fas. Science (New York, N.Y.) 668 7536343
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2010 The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway. Developmental cell 573 21145499
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2005 Regulation of Raf-1 by direct feedback phosphorylation. Molecular cell 497 15664191
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2000 The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01. The Journal of biological chemistry 485 10681541
2010 Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nature medicine 290 20098429
1992 Multiple isoforms of a protein kinase C inhibitor (KCIP-1/14-3-3) from sheep brain. Amino acid sequence of phosphorylated forms. European journal of biochemistry 129 1317796
1997 14-3-3 zeta negatively regulates raf-1 activity by interactions with the Raf-1 cysteine-rich domain. The Journal of biological chemistry 120 9261098
1998 Binding of purified 14-3-3 zeta signaling protein to discrete amino acid sequences within the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex. Biochemistry 116 9425086
2013 Overexpression of YWHAZ relates to tumor cell proliferation and malignant outcome of gastric carcinoma. British journal of cancer 103 23422756
2011 MicroRNA-451 regulates p38 MAPK signaling by targeting of Ywhaz and suppresses the mesangial hypertrophy in early diabetic nephropathy. FEBS letters 92 21827757
1995 Identification of the 14.3.3 zeta domains important for self-association and Raf binding. The Journal of biological chemistry 92 7559537
2017 Involvement of miR-451 in resistance to paclitaxel by regulating YWHAZ in breast cancer. Cell death & disease 90 28981108
2012 14-3-3 zeta as novel molecular target for cancer therapy. Expert opinion on therapeutic targets 84 22512284
2020 The role of YWHAZ in cancer: A maze of opportunities and challenges. Journal of Cancer 83 32127952
2012 A novel function of YWHAZ/β-catenin axis in promoting epithelial-mesenchymal transition and lung cancer metastasis. Molecular cancer research : MCR 83 22912335
1997 Requirement for Drosophila 14-3-3 zeta in Raf-dependent photoreceptor development. Genes & development 81 9159395
2007 Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character. Oncogene 80 17704798
2008 SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via regulation of 14-3-3 zeta and BAD in H9c2 cells. FEBS letters 75 18640115
2003 Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3 zeta. The Biochemical journal 74 12323073
2008 14-3-3 zeta down-regulates p53 in mammary epithelial cells and confers luminal filling. Cancer research 70 18339856
2019 Circ-SERPINE2 promotes the development of gastric carcinoma by sponging miR-375 and modulating YWHAZ. Cell proliferation 62 31199037
2009 Copy number gain and oncogenic activity of YWHAZ/14-3-3zeta in head and neck squamous cell carcinoma. International journal of cancer 57 19405126
2018 LncRNA SNHG14 promotes the progression of cervical cancer by regulating miR-206/YWHAZ. Pathology, research and practice 54 30611620
2003 14-3-3 zeta mediates integrin-induced activation of Cdc42 and Rac. Platelet glycoprotein Ib-IX regulates integrin-induced signaling by sequestering 14-3-3 zeta. The Journal of biological chemistry 54 12810725
2013 Multiple tumor-associated microRNAs modulate the survival and longevity of dendritic cells by targeting YWHAZ and Bcl2 signaling pathways. Journal of immunology (Baltimore, Md. : 1950) 52 23355742
2004 Isoform-specific differences in rapid nucleocytoplasmic shuttling cause distinct subcellular distributions of 14-3-3 sigma and 14-3-3 zeta. Journal of cell science 52 14996909
2019 Long non-coding RNA LUCAT1 promotes proliferation and invasion in gastric cancer by regulating miR-134-5p/YWHAZ axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 48 31545227
1997 14-3-3 zeta protein binds to the carboxyl half of mouse wee1 kinase. Biochemical and biophysical research communications 48 9016762
1995 Differential activation of PKC isozymes by 14-3-3 zeta protein. Biochemical and biophysical research communications 47 7488074
2020 Long noncoding RNA H19 acts as a miR-340-3p sponge to promote epithelial-mesenchymal transition by regulating YWHAZ expression in paclitaxel-resistant breast cancer cells. Environmental toxicology 46 32420678
2018 The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma. Molecular therapy. Nucleic acids 46 29858089
2014 BIS targeting induces cellular senescence through the regulation of 14-3-3 zeta/STAT3/SKP2/p27 in glioblastoma cells. Cell death & disease 46 25412315
2013 Transgenic overexpression of 14-3-3 zeta protects hippocampus against endoplasmic reticulum stress and status epilepticus in vivo. PloS one 44 23359526
2020 G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer. British journal of cancer 43 32989225
2014 Involvement of miR-30c in resistance to doxorubicin by regulating YWHAZ in breast cancer cells. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 40 24519092
2006 The alternative role of 14-3-3 zeta as a sweeper of misfolded proteins in disease conditions. Medical hypotheses 40 16516399
2011 Phosphopeptide-dependent labeling of 14-3-3 ζ proteins by fusicoccin-based fluorescent probes. Angewandte Chemie (International ed. in English) 39 22105970
1999 Residues of 14-3-3 zeta required for activation of exoenzyme S of Pseudomonas aeruginosa. Biochemistry 37 10508420
2021 ITGB1 Drives Hepatocellular Carcinoma Progression by Modulating Cell Cycle Process Through PXN/YWHAZ/AKT Pathways. Frontiers in cell and developmental biology 36 34977001
2015 miR-451 regulates FoxO3 nuclear accumulation through Ywhaz in human colorectal cancer. American journal of translational research 36 26885274
2008 14-3-3 zeta protein secreted by tumor associated monocytes/macrophages from ascites of epithelial ovarian cancer patients. Cancer immunology, immunotherapy : CII 36 18618111
2008 Depletion of 14-3-3 zeta elicits endoplasmic reticulum stress and cell death, and increases vulnerability to kainate-induced injury in mouse hippocampal cultures. Journal of neurochemistry 35 18466333
2021 YWHAZ interacts with DAAM1 to promote cell migration in breast cancer. Cell death discovery 34 34453038
2023 Circ_0069094 regulates malignant phenotype and paclitaxel resistance in breast cancer cells via targeting the miR-136-5p/YWHAZ axis. Thoracic cancer 33 37192740
2019 MiR-451a suppresses cell proliferation, metastasis and EMT via targeting YWHAZ in hepatocellular carcinoma. European review for medical and pharmacological sciences 33 31298411
2010 14-3-3 zeta is a molecular target in guggulsterone induced apoptosis in head and neck cancer cells. BMC cancer 33 21118500
2019 MiRNA-802 suppresses proliferation and migration of epithelial ovarian cancer cells by targeting YWHAZ. Journal of ovarian research 32 31640760
2018 miR-375-3p/YWHAZ/β-catenin axis regulates migration, invasion, EMT in gastric cancer cells. Clinical and experimental pharmacology & physiology 32 30353914
2020 Long noncoding RNA MIR4435-2HG promotes hepatocellular carcinoma proliferation and metastasis through the miR-22-3p/YWHAZ axis. American journal of translational research 31 33194037
2019 Long noncoding RNA LINC00958 promotes the oral squamous cell carcinoma by sponging miR-185-5p/YWHAZ. Life sciences 31 31442551
2010 LC-MS/MS analysis of ovarian cancer metastasis-related proteins using a nude mouse model: 14-3-3 zeta as a candidate biomarker. Journal of proteome research 30 21028892
2002 Immunohistochemical localization of 14.3.3 zeta protein in amyloid plaques in human spongiform encephalopathies. Acta neuropathologica 30 12557018
2021 YY1-modulated long non-coding RNA SNHG12 promotes gastric cancer metastasis by activating the miR-218-5p/YWHAZ axis. International journal of biological sciences 29 33994849
2018 MiR-613 functions as tumor suppressor in hepatocellular carcinoma by targeting YWHAZ. Gene 28 29551505
2013 Somatic copy number alterations by whole-exome sequencing implicates YWHAZ and PTK2 in castration-resistant prostate cancer. The Journal of pathology 28 24114522
2021 circ_C20orf11 enhances DDP resistance by inhibiting miR-527/YWHAZ through the promotion of extracellular vesicle-mediated macrophage M2 polarization in ovarian cancer. Cancer biology & therapy 27 34382916
2020 Circular RNA circNHSL1 Contributes to Gastric Cancer Progression Through the miR-149-5p/YWHAZ Axis. Cancer management and research 27 32848466
2013 Characterization of 14-3-3-ζ Interactions with integrin tails. Journal of molecular biology 27 23763993
2021 MiR-1-3p Suppresses Colorectal Cancer Cell Proliferation and Metastasis by Inhibiting YWHAZ-Mediated Epithelial-Mesenchymal Transition. Frontiers in oncology 26 33718221
2020 Paclitaxel Suppresses Hepatocellular Carcinoma Tumorigenesis Through Regulating Circ-BIRC6/miR-877-5p/YWHAZ Axis. OncoTargets and therapy 26 33061425
2019 A YWHAZ Variant Associated With Cardiofaciocutaneous Syndrome Activates the RAF-ERK Pathway. Frontiers in physiology 26 31024343
2012 The housekeeping gene YWHAZ remains stable in a model of developmentally primed non-alcoholic fatty liver disease. Liver international : official journal of the International Association for the Study of the Liver 26 22583519
2003 Constitutively and autonomously active protein kinase C associated with 14-3-3 zeta in the rodent brain. Journal of neurochemistry 26 12485398
2018 gga-miR-451 Negatively Regulates Mycoplasma gallisepticum (HS Strain)-Induced Inflammatory Cytokine Production via Targeting YWHAZ. International journal of molecular sciences 25 29652844
2016 Ywhaz/14-3-3ζ Deletion Improves Glucose Tolerance Through a GLP-1-Dependent Mechanism. Endocrinology 25 27167773
2015 Transcription factor KLF4 regulates microRNA-544 that targets YWHAZ in cervical cancer. American journal of cancer research 25 26269755
2008 Clinical significance of 14-3-3 zeta in human esophageal cancer. The International journal of biological markers 25 19199271
2010 14-3-3 sigma and 14-3-3 zeta plays an opposite role in cell growth inhibition mediated by transforming growth factor-beta 1. Molecules and cells 24 20082218
2005 Expression of 14-3-3 zeta and interaction with protein kinase C in the rat retina in early diabetes. Diabetologia 24 15909155
2018 YWHAZ promotes ovarian cancer metastasis by modulating glycolysis. Oncology reports 23 30535456
2007 Increases in expression of 14-3-3 eta and 14-3-3 zeta transcripts during neuroprotection induced by delta9-tetrahydrocannabinol in AF5 cells. Journal of neuroscience research 23 17455326
2019 PPIA, HPRT1, and YWHAZ Genes Are Suitable for Normalization of mRNA Expression in Long-Term Expanded Human Mesenchymal Stem Cells. BioMed research international 22 31240211
2018 Anticancer effect of YWHAZ silencing via inducing apoptosis and autophagy in gastric cancer cells. Neoplasma 21 29940752
2016 14-3-3-zeta participates in TLR3-mediated TICAM-1 signal-platform formation. Molecular immunology 21 27058640
2019 YWHAZ amplification/overexpression defines aggressive bladder cancer and contributes to chemo-/radio-resistance by suppressing caspase-mediated apoptosis. The Journal of pathology 20 30945298
2008 Gene-gene interaction between 14-3-3 zeta and butyrylcholinesterase modulates Alzheimer's disease risk. European journal of neurology 20 18290843
2019 MicroRNA-451 inhibits vascular smooth muscle cell migration and intimal hyperplasia after vascular injury via Ywhaz/p38 MAPK pathway. Experimental cell research 19 30930138
2004 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. Neuroscience letters 18 15234461
2002 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. The Journal of biological chemistry 18 11950841
2021 Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway. Frontiers in oncology 17 34195070
2018 YWHAZ Binds to TRIM21 but Is Not Involved in TRIM21-stimulated Osteosarcoma Cell Proliferation. Biomedical and environmental sciences : BES 17 29673441
2011 Identification of a lacosamide binding protein using an affinity bait and chemical reporter strategy: 14-3-3 ζ. Journal of the American Chemical Society 17 21692503
2008 14-3-3 zeta and tau genes interactively decrease Alzheimer's disease risk. Dementia and geriatric cognitive disorders 17 18319590
2022 Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish. Molecular psychiatry 16 35501409
2016 Down-regulation of 14-3-3 Zeta Inhibits TGF-β1-Induced Actomyosin Contraction in Human Trabecular Meshwork Cells Through RhoA Signaling Pathway. Investigative ophthalmology & visual science 16 26906158
2014 Transcriptional regulation of YWHAZ, the gene encoding 14-3-3ζ. PloS one 16 24690670
2024 TMEM65 promotes gastric tumorigenesis by targeting YWHAZ to activate PI3K-Akt-mTOR pathway and is a therapeutic target. Oncogene 15 38341472
2022 YBX1 regulates the survival of chronic myeloid leukemia stem cells by modulating m6A-mediated YWHAZ stability. Cellular oncology (Dordrecht, Netherlands) 15 36512307
2021 PIM1 phosphorylation of the androgen receptor and 14-3-3 ζ regulates gene transcription in prostate cancer. Communications biology 15 34697370
2020 Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues. Journal of ginseng research 15 34295206
2017 14-3-3 α and 14-3-3 ζ contribute to immune responses in planarian Dugesia japonica. Gene 15 28322998
2009 Glial cell type-specific subcellular localization of 14-3-3 zeta: an implication for JCV tropism. Glia 15 19062179
2022 Quercetin acts via the G3BP1/YWHAZ axis to inhibit glycolysis and proliferation in oral squamous cell carcinoma. Toxicology mechanisms and methods 14 35945655
2021 MiRNA-1225 Inhibits Osteosarcoma Tumor Growth and Progression by Targeting YWHAZ. OncoTargets and therapy 14 33442263
2021 The expression of YWHAZ and NDRG1 predicts aggressive outcome in human prostate cancer. Communications biology 14 33483585
2020 Loss of miR-204-5p Promotes Tumor Proliferation, Migration, and Invasion Through Targeting YWHAZ/PI3K/AKT Pathway in Esophageal Squamous Cell Carcinoma. OncoTargets and therapy 14 32547097
2018 MicroRNA-451 blockade promotes osteoblastic differentiation and skeletal anabolic effects by promoting YWHAZ-mediated RUNX2 protein stabilization. MedChemComm 14 30151091
2012 Roles of vimentin and 14-3-3 zeta/delta in the inhibitory effects of heparin on PC-3M cell proliferation and B16-F10-luc-G5 cells metastasis. Acta pharmacologica Sinica 14 22669117
2007 Oxidative damage of 14-3-3 zeta and gamma isoforms in Alzheimer's disease and cerebral amyloid angiopathy. Neuroscience 14 17445990
2022 CircCDK17 knockdown inhibits tumor progression and cell glycolysis by downregulaing YWHAZ expression through sponging miR-1294 in cervical cancer. Journal of ovarian research 13 35168653
2018 MicroRNA-375 Suppresses the Tumor Aggressive Phenotypes of Clear Cell Renal Cell Carcinomas through Regulating YWHAZ. Chinese medical journal 13 30082525
2012 Proteomic analysis of 14-3-3 zeta binding proteins in the mouse hippocampus. International journal of physiology, pathophysiology and pharmacology 13 22837806
2022 14-3-3-zeta mediates GLP-1 receptor agonist action to alter α cell proglucagon processing. Science advances 12 35867787
2018 Down-regulation of 14-3-3 zeta sensitizes human glioblastoma cells to apoptosis induction. Apoptosis : an international journal on programmed cell death 12 30101359