Affinage

YWHAZ

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

Length
245 aa
Mass
27.7 kDa
Annotated
2026-06-11
100 papers in source corpus 42 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YWHAZ (14-3-3 zeta) is a dimeric phosphopeptide-binding scaffold that functions as an integrator of kinase signaling, cytoskeletal dynamics, apoptotic control, and stress responses across many cell types (PMID:7559537, PMID:23763993). It self-assembles into dimers through its amino terminus while its carboxy-terminal half engages client proteins, including c-Raf-1, which it contacts directly at the Raf cysteine-rich domain; this interaction restrains Raf-1 transforming activity yet is required for productive Raf activation in cells and in the Drosophila Ras/Raf/MAPK pathway, placing 14-3-3 zeta upstream of Raf and downstream of Ras (PMID:7559537, PMID:9261098, PMID:9159395). Binding to phosphorylated client motifs is the recurring theme: it associates with diverse substrates such as Wee1, the platelet GP Ib-IX-V complex, and integrin cytoplasmic tails, where phosphorylation enhances binding and a crystal structure resolves both canonical phosphomotif contacts and additional stabilizing surfaces (PMID:9016762, PMID:9425086, PMID:23763993). Through integrin engagement it drives Cdc42/Rac1 activation, cytoskeletal reorganization, and cell spreading, and it further shapes actin dynamics by binding cofilin and LIMK1 and by sustaining RhoA-dependent actomyosin contraction (PMID:12323073, PMID:12810725, PMID:26906158). 14-3-3 zeta suppresses apoptosis by sequestering pro-apoptotic BAD and Bax in the cytoplasm under SIRT2, PP2A, and G3BP1 control, and it down-regulates p53 by driving PI3K/Akt-dependent MDM2 nuclear translocation, conferring anoikis resistance and an early oncogenic role in breast cancer progression (PMID:18339856, PMID:18640115, PMID:21118500, PMID:32989225). It stabilizes beta-catenin by displacing it from beta-TrCP to promote EMT and metastasis, and stabilizes additional clients including RUNX2 in osteoblast differentiation (PMID:22912335, PMID:30151091). A cardiofaciocutaneous syndrome-associated S230W variant acts as a RAS-ERK gain-of-function mutation that escapes casein kinase 1a phosphorylation and binds more Raf (PMID:31024343). Beyond signaling, 14-3-3 zeta shuttles between nucleus and cytoplasm via a Crm1-dependent mechanism, suppresses the unfolded protein response from the ER microsomal compartment to protect neurons, and regulates glucose homeostasis through GLP-1 production in intestinal L cells and islet alpha cells (PMID:14996909, PMID:18466333, PMID:27167773, PMID:23359526). Its own expression is controlled transcriptionally by ATF-1/CREB at a CRE element and post-transcriptionally by m6A-dependent mRNA stabilization through the YBX1–IGF2BP reader complex (PMID:24690670, PMID:36512307).

Mechanistic history

Synthesis pass · year-by-year structured walk · 31 steps
  1. 1992 High

    Establishing the founding biochemical activity: whether 14-3-3 zeta was a kinase regulator and how selective it was defined its functional class.

    Evidence In vitro kinase assays with multiple purified kinases, HPLC isoform separation and direct sequencing of sheep brain protein

    PMID:1317796

    Open questions at the time
    • Did not identify physiological PKC substrates or in-cell relevance
    • Mechanism of inhibition versus the catalytic PKM fragment unresolved
  2. 1995 High

    Resolving the architecture: mapping that dimerization uses the N-terminus while Raf-1 binding uses the C-terminal ~100 residues explained how one protein both oligomerizes and scaffolds clients, and showed 14-3-3 zeta participates in Raf activation.

    Evidence Deletion analysis, two-hybrid, in vitro binding, and COS cell co-expression with Raf stability readout

    PMID:7559537

    Open questions at the time
    • The reported acyltransferase/PLA2 activity not integrated with scaffold role
    • How truncated zeta distinguishes inactive from active Raf unclear
  3. 1995 Medium

    Testing PKC isoform selectivity addressed whether 14-3-3 zeta acts uniformly on kinases; strong cooperative activation of PKC epsilon versus modest classical-isoform effects indicated isoform-specific regulation.

    Evidence In vitro PKC activity assays with purified proteins

    PMID:7488074

    Open questions at the time
    • Single-method in vitro assay without cellular confirmation
    • Structural basis of the high Hill coefficient unexplained
  4. 1997 High

    Defining the Raf binding site and its functional sign: the CRD interaction was shown to be inhibitory, clarifying the dual positive/negative relationship of 14-3-3 zeta to Raf.

    Evidence GST pulldown, Raf-1 CRD mutagenesis, and cell transformation assays

    PMID:9261098

    Open questions at the time
    • How the same protein both inhibits and activates Raf in different contexts not reconciled
    • Phosphorylation dependence of CRD contact not addressed
  5. 1997 High

    Genetic epistasis in Drosophila placed 14-3-3 zeta firmly in the Ras/Raf/MAPK pathway in a living organism, moving beyond biochemistry to developmental requirement.

    Evidence Drosophila loss- and gain-of-function genetics with Raf/Ras epistasis and rescue

    PMID:9159395

    Open questions at the time
    • Molecular target within the pathway in vivo not identified
    • Mammalian developmental requirement not tested here
  6. 1997 Medium

    Identifying Wee1 as a phospho-regulated client extended 14-3-3 zeta scaffolding into cell-cycle kinase regulation.

    Evidence Yeast two-hybrid, in vitro binding, and co-IP from transfected COS-1 cells

    PMID:9016762

    Open questions at the time
    • Functional consequence of Wee1 binding for cell-cycle control not established
    • Endogenous interaction not demonstrated
  7. 1998 High

    Mapping discrete binding sites in the GP Ib-IX-V complex and showing PKA phosphorylation of GP Ibbeta enhances binding established phospho-regulated client engagement at the platelet membrane.

    Evidence Peptide binding assays, Ala-scanning mutagenesis, and immunoprecipitation from platelet extracts

    PMID:9425086

    Open questions at the time
    • Downstream signaling consequence of the platelet interaction defined only later
    • Multiple binding sites of differing affinity not ranked physiologically
  8. 1999 High

    ExoS activation demonstrated that the amphipathic groove serves distinct clients via different residues, separating the Raf-binding determinant (Val-176) from the ExoS-binding surface.

    Evidence Site-directed mutagenesis and in vitro ADP-ribosyltransferase activity assays across isoforms

    PMID:10508420

    Open questions at the time
    • Relevance to host defense in vivo not tested
    • Structural map of the two binding modes incomplete at the time
  9. 2003 High

    Linking 14-3-3 zeta to cofilin/LIMK1 and to integrin-driven Cdc42/Rac1 activation established its role in actin cytoskeletal reorganization and cell spreading, including a sequestration model in platelets.

    Evidence Two-hybrid, GST pulldown, actin co-sedimentation, cell imaging, and CHO rescue with GP Ibalpha constructs

    PMID:12323073 PMID:12810725

    Open questions at the time
    • Phosphorylation control of the integrin tail interactions resolved structurally only later
    • In vivo cytoskeletal phenotype not assessed
  10. 2003 Medium

    Demonstrating that 14-3-3 zeta binds all three PKC subclasses via the C1 domain and confers Ca2+-independent autonomous activity selectively on PKC epsilon connected the early in vitro PKC findings to neuronal contexts.

    Evidence Reciprocal co-IP and kinase activity assays in differentiated PC12 cells and rodent brain

    PMID:12485398

    Open questions at the time
    • Physiological output of autonomous PKC activity not defined
    • Single-lab characterization
  11. 2004 High

    Quantifying nuclear-cytoplasmic shuttling kinetics explained why 14-3-3 zeta has a higher steady-state nuclear presence than other isoforms, identifying a Crm1-dependent export mechanism.

    Evidence FRAP of YFP fusions in multiple cell types with leptomycin B inhibition

    PMID:14996909

    Open questions at the time
    • Nuclear functions driving the higher residence not identified
    • Cargo coupling to shuttling not defined
  12. 2008 High

    Defining the PI3K/Akt/MDM2/p53 axis and BAD sequestration under SIRT2 control established how 14-3-3 zeta restrains apoptosis and confers anoikis resistance, linking it mechanistically to early breast cancer progression.

    Evidence 3D acini cultures with ectopic p53 rescue, transgenic mouse mammary cells, double siRNA epistasis, and subcellular fractionation

    PMID:18339856 PMID:18640115 PMID:36

    Open questions at the time
    • Direct phospho-clients within the PI3K/Akt branch not all mapped
    • Relative contribution of BAD versus p53 arms context-dependent
  13. 2008 Medium

    Identifying ER stress involvement showed that 14-3-3 zeta accumulates in the microsomal fraction and protects neurons from ER stress and excitotoxic injury, broadening its role beyond classical signaling.

    Evidence siRNA knockdown, subcellular fractionation, and organotypic hippocampal cultures with pharmacological ER stress and kainate injury

    PMID:18466333

    Open questions at the time
    • Direct ER client proteins not identified
    • Mechanism of microsomal recruitment unknown
  14. 2010 High

    Connecting YWHAZ to anthracycline resistance and 8q22 amplification gave clinical weight to its anti-apoptotic oncogenic function across patient cohorts.

    Evidence Bidirectional siRNA/overexpression with drug sensitivity assays and integrated genomics in independent cohorts

    PMID:20098429

    Open questions at the time
    • Resistance effector pathways downstream of YWHAZ not fully resolved
    • Causality versus correlation in amplification cohorts limited
  15. 2010 Medium

    Showing 14-3-3 zeta negatively modulates TGF-beta1 growth inhibition via Smad3 linker phosphorylation added a growth-control axis to its scaffold repertoire.

    Evidence Overexpression/knockdown, Smad3 phosphosite mutagenesis, p15 promoter reporter, and cell cycle analysis

    PMID:20082218

    Open questions at the time
    • Whether 14-3-3 zeta directly recruits the relevant Smad3 kinase unclear
    • In vivo relevance not tested
  16. 2012 High

    Establishing the YWHAZ-beta-catenin interaction that blocks beta-TrCP-mediated ubiquitination explained how it stabilizes beta-catenin to drive EMT and metastasis.

    Evidence Co-IP, knockdown, beta-catenin phosphosite mutants, invasion/migration and in vivo tumorigenesis assays

    PMID:22912335

    Open questions at the time
    • Stoichiometry of the displacement of beta-TrCP not quantified
    • Structural basis of S552-dependent complex formation undefined
  17. 2013 Medium

    Demonstrating that knockdown activates JNK/p38 and enforces cell-cell adhesion clarified isoform-specific oncogenic functions that restrain stress apoptosis and adhesion.

    Evidence siRNA knockdown with apoptosis, JNK/p38 signaling, and adhesion protein readouts

    PMID:17704798

    Open questions at the time
    • Direct clients linking 14-3-3 zeta to JNK/p38 not identified
    • Single-lab phenotypic study
  18. 2013 High

    Transgenic overexpression confirmed in vivo that 14-3-3 zeta down-regulates UPR components and protects against ER stress and seizure-induced neuronal death.

    Evidence Transgenic mouse overexpression with tunicamycin and status epilepticus injury models and UPR pathway analysis

    PMID:23359526

    Open questions at the time
    • Molecular target controlling UPR component levels not identified
    • Whether effect is cell-autonomous in neurons unresolved
  19. 2013 High

    Crystallography of the integrin alpha4 tail complex resolved both canonical phosphomotif and accessory contacts, defining the structural rules of phospho-dependent client engagement.

    Evidence X-ray crystallography, ITC, NMR, and mutagenesis across integrin tail variants

    PMID:23763993

    Open questions at the time
    • Functional ranking of the multiple integrin tail interactions in cells incomplete
    • Phosphorylation-independent contacts mechanistically uncharacterized
  20. 2014 High

    Identifying ATF-1/CREB control at a CRE element defined how YWHAZ transcription is regulated and induced under TNF-alpha stimulation.

    Evidence 5' RACE, EMSA, ChIP, reporter assays, and ATF-1 siRNA knockdown

    PMID:24690670

    Open questions at the time
    • Upstream signals converging on the CRE not fully mapped
    • Transcript-variant-specific functions not resolved
  21. 2014 Medium

    Showing PP2A-mediated BAD release and STAT3/SKP2/p27 dependence linked 14-3-3 zeta to senescence control and the intrinsic mitochondrial apoptosis pathway.

    Evidence Co-IP, bidirectional manipulation with rescue, fractionation, and apoptosis/senescence markers in HNSCC and glioblastoma cells

    PMID:21118500 PMID:25412315

    Open questions at the time
    • Direct STAT3 binding by 14-3-3 zeta not demonstrated
    • Single-lab pathways not independently confirmed
  22. 2016 Medium

    Placing 14-3-3 zeta upstream of RhoA in actomyosin contraction and within TLR3-TICAM-1 innate immune signaling extended its scaffold role to ECM remodeling and interferon responses.

    Evidence siRNA knockdown with RhoA activation, MLC/cofilin phosphorylation, contraction assays, and TICAM-1 multimerization/IRF3 translocation readouts

    PMID:26906158 PMID:27058640

    Open questions at the time
    • Direct clients controlling RhoA levels and TICAM-1 assembly not identified
    • Single-lab mechanistic placements
  23. 2016 High

    Knockout mouse and L-cell studies established that 14-3-3 zeta regulates glucose homeostasis through a GLP-1-dependent mechanism, a metabolic role distinct from its signaling functions.

    Evidence Ywhaz knockout mice, glucose tolerance tests, GLP-1 measurement, GLUTag knockdown, and GLP-1R antagonist rescue

    PMID:27167773

    Open questions at the time
    • Molecular clients controlling proglucagon processing not identified here
    • Tissue-specific contributions not dissected
  24. 2018 Medium

    Showing YWHAZ stabilizes RUNX2 to promote osteoblast differentiation added a protein-stabilization function relevant to bone formation.

    Evidence miR-451 manipulation, knockdown, RUNX2 stability blotting, and OVX mouse bone morphometry

    PMID:30151091

    Open questions at the time
    • Whether YWHAZ binds RUNX2 directly not demonstrated
    • Mechanism of stabilization undefined
  25. 2018 Medium

    Identifying TRIM21 as an E3 ligase that promotes YWHAZ degradation began to define how YWHAZ protein levels are post-translationally controlled.

    Evidence Co-IP with LC-MS/MS, BiFC, RING-deletion constructs, and proliferation assays

    PMID:29673441

    Open questions at the time
    • YWHAZ ubiquitination sites not mapped
    • No functional consequence of TRIM21-driven YWHAZ turnover in the tested proliferation pathway
  26. 2019 High

    The CFC syndrome S230W variant established a direct human disease link and revealed a gain-of-function mechanism in RAS-ERK signaling, distinguishing it from wild-type Raf regulation.

    Evidence Xenopus embryo overexpression, dominant-negative FGFR rescue, ERK phosphorylation, Raf co-IP, and casein kinase 1a phosphorylation assays

    PMID:31024343

    Open questions at the time
    • Mammalian/patient cellular phenotype not directly characterized
    • How escape from CK1a phosphorylation increases Raf binding mechanistically unresolved
  27. 2021 High

    PIM1-dependent phosphorylation coupling YWHAZ to androgen receptor on chromatin defined a transcriptional co-regulatory function at migration/invasion genes with hnRNPK and TRIM28.

    Evidence Co-IP, ChIP-seq, RIME, and gene expression analysis in PIM1-overexpressing cells

    PMID:34697370

    Open questions at the time
    • Whether chromatin association is direct or scaffold-mediated unclear
    • Generalizability beyond PIM1-high cells untested
  28. 2021 Medium

    Identifying DAAM1, G3BP1, and TMEM65 as YWHAZ partners connected it to microfilament/RhoA remodeling, Bax sequestration, and PI3K-Akt-mTOR-driven tumorigenesis with regulated YWHAZ stability.

    Evidence Co-IP, colocalization, RhoA and Bax localization readouts, protein stability assays, and xenograft models across cancer types

    PMID:32989225 PMID:34453038 PMID:38341472

    Open questions at the time
    • Direct phospho-dependence of these interactions not all established
    • Single-lab interaction studies needing reciprocal validation
  29. 2022 High

    Establishing m6A-dependent YWHAZ mRNA stabilization by YBX1/IGF2BP defined the post-transcriptional control that sustains YWHAZ in leukemia stem cells.

    Evidence RIP, RNA decay assays, CRISPR KO with YWHAZ rescue, and a CML mouse model

    PMID:36512307

    Open questions at the time
    • Specific m6A sites on YWHAZ mRNA not all mapped
    • Whether this regulation operates outside CML untested
  30. 2022 High

    Zebrafish knockout linked ywhaz to monoaminergic neurotransmission and neuronal connectivity, and islet studies tied it to alpha-cell proglucagon processing, deepening its neural and metabolic physiology.

    Evidence CRISPR zebrafish KO with whole-brain imaging, monoamine quantification and pharmacological rescue; mouse/human islet alpha-cell ablation with liraglutide

    PMID:35501409 PMID:35867787

    Open questions at the time
    • Molecular clients mediating monoaminergic and paracrine effects not identified
    • Mechanistic continuity between neural and metabolic roles unestablished
  31. 2022 High

    Small-molecule co-crystal structures with PPD and prior probes mapped druggable surface residues and demonstrated stabilization of 14-3-3 zeta/phosphopeptide interactions.

    Evidence Co-crystallography, ITC, biolayer interferometry, mutagenesis, and fusicoccin/lacosamide chemical biology

    PMID:21692503 PMID:22105970 PMID:34295206

    Open questions at the time
    • Therapeutic consequences of modulating these surfaces not established
    • Endogenous ligands at these sites largely uncharacterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the hundreds of client interactions are selected, prioritized, and dynamically regulated to produce distinct cell-type-specific outcomes remains the central open question.
  • No unified model linking phospho-client selection to context-specific physiological output
  • Reconciliation of opposing Raf inhibition versus activation roles unresolved
  • Direct versus scaffold-mediated nature of many reported interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 3
Localization
GO:0005829 cytosol 4 GO:0005634 nucleus 3 GO:0005783 endoplasmic reticulum 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-168256 Immune System 1
Partners
ARBADCFL1CTNNB1DAAM1LIMK1RAF1WEE1

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 YWHAZ (KCIP-1/14-3-3 zeta) from sheep brain is an inhibitor of protein kinase C (PKC); however, it shows no inhibitory activity toward the catalytic fragment of PKC (protein kinase M), and has no effect on cAMP-dependent protein kinase, Ca2+/calmodulin-dependent protein kinase II, or casein kinase 2. Four isoforms of KCIP-1 are substrates for PKC phosphorylation in vitro. N-termini are acetylated and secondary structure is predominantly alpha-helical and amphipathic. In vitro kinase assays, reverse-phase HPLC isoform separation, direct protein sequencing, secondary structure prediction European journal of biochemistry High 1317796
1995 14-3-3 zeta self-assembles into dimers via its amino-terminal sequences, while the carboxy-terminal ~100 amino acids mediate binding to c-Raf-1. 14-3-3 zeta is also an arachidonate-selective acyltransferase and putative phospholipase A2. Truncated 14-3-3 zeta that binds Raf but lacks full-length structure associates only with inactive Raf, indicating 14-3-3 participates in Raf activation. Overexpression of 14-3-3 zeta stabilizes recombinant Raf polypeptide levels. Deletion analysis, in vitro binding assays, two-hybrid analysis, COS cell co-expression, kinase activity assays The Journal of biological chemistry High 7559537
1995 14-3-3 zeta differentially activates PKC isoforms: classical PKC isoforms show ~2-fold activation, PKC delta shows no significant increase, while PKC epsilon is highly activated with strong positive cooperativity (Hill coefficient ~6). In vitro PKC activity assay with purified proteins Biochemical and biophysical research communications Medium 7488074
1997 14-3-3 zeta binds directly to the Raf-1 cysteine-rich domain (CRD, residues 139–184). Mutation of Raf-1 residues 143–145 impairs 14-3-3 binding but not Ras binding. Introduction of these mutations into full-length Raf-1 results in enhanced transforming activity, indicating that 14-3-3 interaction with the Raf-CRD negatively regulates Raf-1 function. GST pulldown, mutagenesis, transformation assays The Journal of biological chemistry High 9261098
1997 Drosophila 14-3-3 zeta (D14-3-3 zeta) is an essential component of the Ras/Raf/MAPK signaling pathway required for photoreceptor differentiation, acting upstream of Raf and downstream of Ras, as established by genetic epistasis with gain-of-function Raf and Ras alleles. Drosophila genetics, loss-of-function mutant analysis, gain-of-function epistasis rescue experiments, in situ expression and subcellular localization Genes & development High 9159395
1997 14-3-3 zeta binds to the carboxyl half of mouse Wee1 kinase, as demonstrated by yeast two-hybrid screening, in vitro binding of recombinant proteins, and co-immunoprecipitation from COS-1 cells co-transfected with both proteins. Wee1 phosphorylated by Cdc2 kinase also binds 14-3-3 zeta. Both the entire kinase domain and a carboxyl-terminal sequence of Wee1 are required for binding. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation from transfected cells Biochemical and biophysical research communications Medium 9016762
1998 Purified 14-3-3 zeta binds to discrete amino acid sequences within the cytoplasmic domain of the platelet GP Ib-IX-V complex, including the C-terminal GHSL sequence of GP Ibalpha, a central region of GP Ibalpha (Arg557–Gly575), and sequences in GP Ibbeta (Arg160–Arg175) and GP V (Lys529–Gly544). Phosphorylation of GP Ibbeta at Ser166 (a PKA site) enhances 14-3-3 zeta binding affinity ~8-fold. Soluble peptides based on these sequences partially displace 14-3-3 zeta from GP Ib-IX-V in platelet extracts by immunoprecipitation. Peptide immobilization binding assay, radiolabeled protein binding with competition, Ala-scanning mutagenesis, immunoprecipitation from platelet extracts Biochemistry High 9425086
1999 14-3-3 zeta activates the ADP-ribosyltransferase activity of Pseudomonas aeruginosa ExoS; this activation requires basic residues lining the amphipathic groove of 14-3-3 zeta. Mutations of Val-176 that disrupt Raf-1 binding do not affect ExoS binding/activation, indicating ExoS uses distinct residues in the Raf-binding groove. Multiple 14-3-3 isoforms (beta, zeta, eta, sigma, tau) activate ExoS with similar efficiency, implicating a conserved structural element. Site-directed mutagenesis, in vitro ADP-ribosyltransferase activity assay, binding assays Biochemistry High 10508420
2003 14-3-3 zeta interacts with the actin-depolymerizing factor cofilin and its regulatory kinase LIMK1, as shown by yeast two-hybrid and GST pulldown. Deletion analysis identified consensus 14-3-3 binding sites on both cofilin and LIMK1. The C-terminal region of 14-3-3 zeta inhibits cofilin binding to actin in co-sedimentation assays. Upon co-transfection, 14-3-3 zeta immunoreactivity redistributes into LIMK1-induced actin aggregations in COS-7 cells. Yeast two-hybrid, GST pulldown, co-sedimentation assay, co-transfection and immunolocalization The Biochemical journal High 12323073
2003 14-3-3 zeta mediates integrin-induced activation of Cdc42 and Rac1 and subsequent cytoskeletal reorganization and cell spreading. In platelets, GP Ibalpha sequesters 14-3-3 zeta via its cytoplasmic domain, thereby regulating integrin-induced signaling; expression of 14-3-3 zeta restores Rho GTPase activation and spreading in cells expressing truncated GP Ibalpha lacking the 14-3-3 zeta binding site. CHO cell transfection with GP Ibalpha constructs, Cdc42/Rac activation assays, cytoskeletal reorganization assays, rescue by 14-3-3 zeta expression The Journal of biological chemistry High 12810725
2003 In neuronally differentiated PC12 cells and rodent brain, three PKC subclasses (classical, novel, and atypical) all interact with 14-3-3 zeta. The 14-3-3 zeta-associated PKC pool exhibits constitutive and autonomous Ca2+-independent activity. The C1 domain of PKC is involved in binding. The association of 14-3-3 zeta has distinct effects on different PKC classes: the classical PKC-alpha associated with 14-3-3 zeta shows no autonomous activity whereas non-classical PKC-epsilon does. Immunoprecipitation, co-immunoprecipitation, kinase activity assays, stable FLAG-tagged 14-3-3 zeta cell line Journal of neurochemistry Medium 12485398
2004 14-3-3 zeta and 14-3-3 sigma have distinct subcellular distributions due to differences in nuclear export rate: 14-3-3 sigma has a 1.7x higher nuclear export rate constant than 14-3-3 zeta, while nuclear import rates are equal. Both isoforms shuttle rapidly in and out of the nucleus via a Crm1-dependent, leptomycin B-sensitive mechanism. At steady state, 14-3-3 zeta is present at relatively higher levels in the nucleus than 14-3-3 sigma. FRAP of YFP-fusion proteins in multiple mammalian cell types, leptomycin B inhibition, isoform-specific antibody staining Journal of cell science High 14996909
2008 14-3-3 zeta down-regulates p53 in mammary epithelial cells by inducing hyperactivation of the PI3K/Akt pathway, which leads to phosphorylation and nuclear translocation of the MDM2 E3 ligase, resulting in increased p53 degradation. This mechanism confers resistance to anoikis and luminal filling in 3D acini cultures. Ectopic p53 expression restores luminal apoptosis in 14-3-3 zeta-overexpressing acini. 3D culture model, western blotting, transgenic mouse mammary epithelial cells, ectopic p53 rescue, PI3K/Akt pathway analysis Cancer research High 18339856
2008 SIRT2 knockdown induces expression of 14-3-3 zeta, which facilitates cytosolic sequestration of BAD, reducing mitochondrial BAD localization and conferring cytoprotection against anoxia-reoxygenation injury. Concurrent siRNA knockdown of both SIRT2 and 14-3-3 zeta abolishes the cytoprotective phenotype, placing 14-3-3 zeta downstream of SIRT2 in this pathway. siRNA knockdown (single and double), gene array, subcellular fractionation, H9c2 cell anoxia-reoxygenation model FEBS letters High 18640115
2008 Depletion of 14-3-3 zeta in mouse organotypic hippocampal cultures using siRNA induces ER stress proteins and granule cell death. Under ER stress (tunicamycin), 14-3-3 zeta accumulates in the ER-containing microsomal fraction. Kainic acid-induced damage is significantly increased in cultures with 14-3-3 zeta siRNA knockdown, demonstrating a neuroprotective role of 14-3-3 zeta in ER stress and seizure injury. siRNA knockdown, subcellular fractionation, organotypic hippocampal cultures, pharmacological ER stress induction Journal of neurochemistry Medium 18466333
2010 siRNA-mediated knockdown of YWHAZ sensitizes breast tumor cells to anthracyclines (doxorubicin), while overexpression induces anthracycline resistance. YWHAZ overexpression and amplification on chromosome 8q22 are associated with early disease recurrence despite adjuvant anthracycline treatment. siRNA knockdown, overexpression in cell lines, drug sensitivity assays, integrated genomics across independent cohorts Nature medicine High 20098429
2011 Fusicoccin-based cell-penetrating fluorescent probes form ternary complexes with 14-3-3 zeta proteins and phosphopeptide ligands, whereupon the probes site-specifically attach a fluorescent tag to the surface of 14-3-3 zeta. This demonstrates that fusicoccin stabilizes 14-3-3 zeta/phosphopeptide interactions. Chemical biology/affinity labeling, fluorescent probe-based ternary complex formation Angewandte Chemie (International ed. in English) Medium 22105970
2011 14-3-3 zeta is identified as a binding protein for the antiepileptic drug lacosamide in rodent brain lysates, with adduction occurring at K120. Binding is stereospecific and depends on endogenous xanthine. Competition experiments confirm that lacosamide binds at or near the modification site on 14-3-3 zeta. Direct 14-3-3 zeta–xanthine interaction was confirmed by isothermal calorimetry. Affinity bait and chemical reporter strategy, mass spectrometry identification of adduction site, isothermal calorimetry, competition binding assays Journal of the American Chemical Society High 21692503
2012 YWHAZ promotes epithelial-mesenchymal transition (EMT) and lung cancer metastasis through interaction with beta-catenin. YWHAZ binds beta-catenin (co-IP), reduces ubiquitinated beta-catenin by disassociating beta-catenin from beta-TrCP, and facilitates beta-catenin accumulation in cytosol and nucleus activating beta-catenin-mediated transcription. S552 phosphorylation of beta-catenin increases the beta-catenin/YWHAZ complex, promoting invasiveness. Co-immunoprecipitation, siRNA/shRNA knockdown, dominant-negative and dominant-positive beta-catenin mutant expression, invasion/migration assays, in vivo tumorigenesis Molecular cancer research : MCR High 22912335
2013 14-3-3 zeta knockdown sensitizes cells to stress-induced apoptosis and activates JNK/p38 signalling, and also enforces cell-cell contacts and expression of adhesion proteins, revealing isoform-specific oncogenic functions that restrain apoptosis and cell adhesion. siRNA knockdown, apoptosis assays, JNK/p38 signaling assays, adhesion protein expression analysis Oncogene Medium 17704798
2013 14-3-3 zeta binds to integrin alpha4 cytoplasmic tail in a canonical phospho-dependent manner (X-ray crystal structure obtained), but with additional contacts outside the consensus 14-3-3 binding motif essential for efficient interaction. Beta2 integrin short phospho-peptide is sufficient for high-affinity binding. Novel phosphorylation-independent interactions with integrin tails are also reported. The strongest interaction is with the beta1A integrin tail variant. X-ray crystallography of 14-3-3 zeta/alpha4-phosphopeptide complex, ITC, NMR, mutagenesis, biophysical characterization Journal of molecular biology High 23763993
2014 Guggulsterone treatment releases BAD from the inhibitory action of 14-3-3 zeta in HNSCC cells by activating protein phosphatase 2A (PP2A), which initiates the intrinsic mitochondrial apoptosis pathway (cytochrome c release, caspase activation, PARP cleavage). This demonstrates that 14-3-3 zeta sequesters BAD to prevent apoptosis and PP2A can disrupt this interaction. Co-immunoprecipitation, western blotting, apoptosis assays (annexin V, DNA fragmentation), caspase activity, cytochrome c fractionation BMC cancer Medium 21118500
2014 14-3-3 zeta expression is transcriptionally regulated by ATF-1 and CREB binding to a functional Cyclic-AMP Response Element (CRE) in the proximal promoter of the predominant YWHAZ transcript variant (1c). Silencing ATF-1 markedly reduces two of five YWHAZ transcript variants. ATF-1 (and to a lesser extent CREB) binds the endogenous YWHAZ promoter especially under TNF-alpha stimulation. 5' RACE, promoter identification, EMSA, ChIP, cell-based reporter assays, ATF-1 siRNA knockdown PloS one High 24690670
2014 BIS depletion induces cellular senescence in glioblastoma cells through a pathway involving decreased 14-3-3 zeta expression. 14-3-3 zeta depletion per se induces senescence, and ectopic 14-3-3 zeta expression blocks BIS-depletion-induced senescence. 14-3-3 zeta supports STAT3 solubility/activity, with its loss causing STAT3 accumulation in the insoluble fraction, decreased SKP2 transcription, and subsequent p27 accumulation leading to G1 arrest. siRNA knockdown, ectopic overexpression rescue, western blotting with fractionation, senescence assays Cell death & disease Medium 25412315
2016 14-3-3 zeta knockdown in trabecular meshwork (TM) cells decreases phosphorylation of myosin light chain (MLC) and cofilin, reduces stress fiber and focal adhesion formation, alters ECM mRNA composition, and inhibits TGF-beta1-induced cell contraction. Silencing of 14-3-3 zeta directly decreases total RhoA levels, placing 14-3-3 zeta upstream of RhoA in the actomyosin contraction pathway. siRNA knockdown, western blotting, immunofluorescence, collagen gel contraction assay, RhoA activation assay, RT-PCR Investigative ophthalmology & visual science Medium 26906158
2016 14-3-3 zeta participates in TLR3-TICAM-1 innate immune signaling. Knockdown of 14-3-3 zeta reduces type I interferon production, inflammatory cytokine production, IRF3 nuclear translocation, IκB phosphorylation, and inhibits TICAM-1 multimerization following TLR3 ligand stimulation, indicating 14-3-3 zeta promotes TICAM-1 signalosome formation. siRNA knockdown, TICAM-1 multimerization assay, IRF3 nuclear translocation assay, cytokine production measurement Molecular immunology Medium 27058640
2016 Ywhaz gene knockout mice (14-3-3 zeta KO) exhibit improved oral glucose tolerance associated with elevated fasting GLP-1 levels. 14-3-3 zeta knockdown in GLUTag L cells elevates GLP-1 synthesis and release. Systemic GLP-1 receptor inhibition attenuates improved oral glucose tolerance in 14-3-3 zeta KO mice, demonstrating that 14-3-3 zeta regulates glucose homeostasis through a GLP-1-dependent mechanism in intestinal L cells. Ywhaz knockout mouse, oral and IP glucose tolerance tests, GLP-1 measurement, siRNA knockdown in GLUTag cells, GLP-1 receptor antagonist treatment Endocrinology High 27167773
2019 A YWHAZ variant S230W identified in patients with cardiofaciocutaneous (CFC) syndrome acts as a gain-of-function mutation in the RAS-ERK pathway. In Xenopus laevis, S230W induces severe embryonic defects, rescues dominant negative FGF receptor defects more efficiently than wild-type, enhances Raf-stimulated Erk phosphorylation, binds more Raf, and escapes phosphorylation by casein kinase 1a. Neither YWHAZ nor the variant promotes membrane recruitment of Raf. Xenopus embryo overexpression, dominant-negative FGF receptor rescue assay, ERK phosphorylation assay, co-immunoprecipitation for Raf binding, casein kinase 1a phosphorylation assay Frontiers in physiology High 31024343
2021 YWHAZ interacts 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, and blocking the YWHAZ-DAAM1 complex inhibits breast cancer cell migration. Co-immunoprecipitation, immunofluorescence colocalization, RhoA activation assay, miR-613 overexpression, cell migration assay Cell death discovery Medium 34453038
2021 PIM1 phosphorylates 14-3-3 zeta, which coordinates its interaction with androgen receptor (AR, also phosphorylated by PIM1 at S213). PIM1 phosphorylation of both AR and 14-3-3 zeta causes their extensive co-occupancy of chromatin at genes involved in cell migration and invasion, resulting in PIM1-dependent increase in expression of these genes. RIME identifies hnRNPK and TRIM28 as additional co-regulators interacting with both AR and 14-3-3 zeta in PIM1-overexpressing cells. Co-immunoprecipitation, ChIP-seq, RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins), gene expression analysis Communications biology High 34697370
2021 TMEM65 directly binds YWHAZ in the cytoplasm and inhibits ubiquitin-mediated degradation of YWHAZ, thereby stabilizing YWHAZ protein and activating the PI3K-Akt-mTOR signaling pathway to promote gastric cancer tumorigenesis. TMEM65 oncogenic effects are partly dependent on YWHAZ. Co-immunoprecipitation, western blotting, siRNA knockdown, xenograft model, protein stability assays Oncogene Medium 38341472
2022 YBX1 cooperates with RNA m6A reader IGF2BPs to stabilize YWHAZ mRNA in an m6A-dependent manner in CML cells. Loss of YBX1 decreases YWHAZ expression by accelerating YWHAZ mRNA decay. Restoration of YWHAZ rescues defects caused by YBX1 deficiency, establishing YWHAZ as a key downstream effector of YBX1 in CML leukemia stem cell survival. RNA immunoprecipitation, co-immunoprecipitation, RNA decay assay, RNA sequencing, CRISPR/Cas9 KO, CML mouse model Cellular oncology High 36512307
2022 ywhaz deficiency in zebrafish alters neuronal activity and connectivity in the hindbrain. Adult ywhaz KO fish show decreased monoamine levels in the hindbrain and freezing behavior in response to novel stimuli. This behavioral phenotype is reversed by drugs targeting monoamine neurotransmission, suggesting 14-3-3 zeta regulates monoaminergic neurotransmission and neuronal connectivity. CRISPR/Cas9 knockout in zebrafish, whole-brain light-sheet imaging, monoamine quantification, pharmacological rescue, behavioral testing Molecular psychiatry High 35501409
2022 14-3-3 zeta is identified as a target protein of ginsenoside metabolite 20(S)-protopanaxadiol (PPD) in brain tissue. Co-crystal structure of 14-3-3 zeta–PPD shows main interactions with residues R56, R127, and Y128. Mutagenesis of any of these residues significantly decreases affinity between PPD and 14-3-3 zeta. Affinity chromatography, biolayer interferometry, isothermal titration calorimetry, X-ray co-crystallography, site-directed mutagenesis Journal of ginseng research High 34295206
2022 14-3-3-zeta in islets mediates the effect of GLP-1 receptor agonist liraglutide on alpha cell proglucagon processing. The effect of beta cell GLP-1R signaling to activate alpha cell GLP-1 expression is mediated by a secreted protein factor regulated by 14-3-3-zeta. Alpha cell ablation blunts the ability of liraglutide to enhance glucose-stimulated insulin secretion. Mouse and human islet studies, alpha cell ablation model, liraglutide treatment, GLP-1 measurement, paracrine signaling assays Science advances Medium 35867787
2018 YWHAZ promotes osteoblastic differentiation by stabilizing RUNX2 protein. miR-451 blockade de-represses YWHAZ expression, which enhances RUNX2 protein stability and promotes osteoblastic differentiation and bone formation in vitro and in vivo. YWHAZ knockdown reduces RUNX2 stability and osteoblastic phenotype markers. miR-451 agomir/antagomir transfection, YWHAZ knockdown, western blotting for RUNX2 stability, OVX mouse in vivo model, bone morphometry MedChemComm Medium 30151091
2010 14-3-3 zeta overexpression in mammary epithelial cells (MCF10A) in 3D culture causes luminal filling by conferring resistance to anoikis. 14-3-3 zeta overexpression begins at the atypical ductal hyperplasia stage of breast disease, establishing it as an early event in breast cancer progression. 3D acini culture, MCF10A overexpression, anoikis assay, transgenic mouse mammary cells, histological staging of patient samples Cancer research High 18339856
2005 In the diabetic rat retina, the direct interaction between 14-3-3 zeta and PKC is markedly decreased after 6 weeks of diabetes, while PKC activity is increased, suggesting that reduced 14-3-3 zeta levels contribute to PKC activation in diabetic retinopathy. Western blot, Northern blot, immunoprecipitation, double immunostaining, PKC activity assay Diabetologia Medium 15909155
2010 14-3-3 zeta negatively modulates TGF-beta1-mediated growth inhibition. Overexpression of 14-3-3 zeta increases the level of Smad3 phosphorylated at linker regions (which cannot mediate TGF-beta1 growth inhibitory response). Mutation of the 14-3-3 zeta phosphorylation sites in Smad3 reduces the 14-3-3 zeta-mediated inhibition of TGF-beta1-induced p15 promoter activity and cell cycle arrest. siRNA knockdown, overexpression, Smad3 phosphorylation analysis, promoter-reporter assay, Smad3 mutagenesis, cell cycle analysis Molecules and cells Medium 20082218
2013 Transgenic overexpression of 14-3-3 zeta in mice selectively down-regulates unfolded protein response (UPR) pathway components in hippocampus (GRP78, GRP94, ATF4, ATF6, Xbp1 splicing) and potently protects against neuronal death caused by ER stress (tunicamycin) and prolonged seizures, demonstrating a direct role in neuronal survival through ER stress regulation. Transgenic mouse overexpression, tunicamycin ER stress model, status epilepticus model, histological cell death quantification, UPR protein expression analysis PloS one High 23359526
2021 G3BP1 interacts with YWHAZ to sequester Bax in the cytoplasm, thereby suppressing pro-apoptotic signaling and promoting chemoresistance in gastric cancer cells. G3BP1 knockdown increases sensitivity to chemotherapy drugs and elevates apoptosis; co-expression analysis identifies YWHAZ as the critical molecular intermediary. Co-immunoprecipitation, immunoprecipitation, immunofluorescence, siRNA knockdown, drug sensitivity assays British journal of cancer Medium 32989225
2018 YWHAZ binds TRIM21 (E3 ubiquitin ligase) as a novel interaction partner, and TRIM21's RING domain negatively regulates YWHAZ expression levels (i.e., TRIM21 promotes YWHAZ degradation). However, YWHAZ overexpression does not affect TRIM21-stimulated osteosarcoma cell proliferation (negative result for YWHAZ in this specific TRIM21 proliferation pathway). Co-immunoprecipitation with LC-MS/MS, bimolecular fluorescence complementation, TRIM21-ΔRING construct, MTT assay Biomedical and environmental sciences : BES Medium 29673441
2012 Proteomic pulldown of recombinant His-tagged 14-3-3 zeta from mouse hippocampus identifies 13 known 14-3-3 binding partners and 16 novel interacting proteins. 14-3-3 zeta distributes to cytoplasm, microsomal, nuclear, and mitochondrial fractions of the mouse hippocampus. His-tagged pulldown, LC-MS/MS, subcellular fractionation International journal of physiology, pathophysiology and pharmacology Low 22837806

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nature medicine 291 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 93 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
2020 The role of YWHAZ in cancer: A maze of opportunities and challenges. Journal of Cancer 85 32127952
2012 14-3-3 zeta as novel molecular target for cancer therapy. Expert opinion on therapeutic targets 84 22512284
2012 A novel function of YWHAZ/β-catenin axis in promoting epithelial-mesenchymal transition and lung cancer metastasis. Molecular cancer research : MCR 84 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
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 47 32420678
2018 The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma. Molecular therapy. Nucleic acids 47 29858089
2014 BIS targeting induces cellular senescence through the regulation of 14-3-3 zeta/STAT3/SKP2/p27 in glioblastoma cells. Cell death & disease 47 25412315
1995 Differential activation of PKC isozymes by 14-3-3 zeta protein. Biochemical and biophysical research communications 47 7488074
2020 G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer. British journal of cancer 45 32989225
2013 Transgenic overexpression of 14-3-3 zeta protects hippocampus against endoplasmic reticulum stress and status epilepticus in vivo. PloS one 44 23359526
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
2021 ITGB1 Drives Hepatocellular Carcinoma Progression by Modulating Cell Cycle Process Through PXN/YWHAZ/AKT Pathways. Frontiers in cell and developmental biology 37 34977001
1999 Residues of 14-3-3 zeta required for activation of exoenzyme S of Pseudomonas aeruginosa. Biochemistry 37 10508420
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
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 30 33994849
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
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
2020 Paclitaxel Suppresses Hepatocellular Carcinoma Tumorigenesis Through Regulating Circ-BIRC6/miR-877-5p/YWHAZ Axis. OncoTargets and therapy 27 33061425
2013 Characterization of 14-3-3-ζ Interactions with integrin tails. Journal of molecular biology 27 23763993
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 27 22583519
2021 MiR-1-3p Suppresses Colorectal Cancer Cell Proliferation and Metastasis by Inhibiting YWHAZ-Mediated Epithelial-Mesenchymal Transition. Frontiers in oncology 26 33718221
2019 A YWHAZ Variant Associated With Cardiofaciocutaneous Syndrome Activates the RAF-ERK Pathway. Frontiers in physiology 26 31024343
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
2018 YWHAZ promotes ovarian cancer metastasis by modulating glycolysis. Oncology reports 25 30535456
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
2016 14-3-3-zeta participates in TLR3-mediated TICAM-1 signal-platform formation. Molecular immunology 23 27058640
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 YWHAZ amplification/overexpression defines aggressive bladder cancer and contributes to chemo-/radio-resistance by suppressing caspase-mediated apoptosis. The Journal of pathology 22 30945298
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
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
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 18 34195070
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
2022 Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish. Molecular psychiatry 17 35501409
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
2024 TMEM65 promotes gastric tumorigenesis by targeting YWHAZ to activate PI3K-Akt-mTOR pathway and is a therapeutic target. Oncogene 16 38341472
2022 Quercetin acts via the G3BP1/YWHAZ axis to inhibit glycolysis and proliferation in oral squamous cell carcinoma. Toxicology mechanisms and methods 16 35945655
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
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
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

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