Affinage

NFATC4

Nuclear factor of activated T-cells, cytoplasmic 4 · UniProt Q14934

Length
902 aa
Mass
95.4 kDa
Annotated
2026-04-29
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFATc4 is a calcium/calcineurin-regulated transcription factor that integrates diverse extracellular signals to control gene expression programs in the heart, brain, immune cells, adipocytes, and liver. In resting cells, NFATc4 is maintained in the cytoplasm by phosphorylation at gate-keeping residues Ser168/170 by kinases including p38, mTOR, ERK5, and GSK-3β; calcium influx through L-type channels or store-operated Orai1 channels activates calcineurin, which dephosphorylates NFATc4 to drive its nuclear translocation, where it activates or represses target genes (including BDNF, Kv4.2, GABRA2/4, CYP11B2, BACE1, PPARγ2, BNP, and GAP-43) through cooperation with cofactors such as CBP, GATA-4, FoxP1, myocardin, and estrogen receptors (PMID:10537109, PMID:11997522, PMID:18347059, PMID:11514544, PMID:21606195). Nuclear export and degradation are enforced by rephosphorylation cascades (GSK-3β/ERK5/CK1α priming, RSK/ERK1/2 at Ser676, CDK3 at Ser259) and by GSK-3β-triggered K48-linked polyubiquitination, while SIRT2- and SIRT6-mediated deacetylation and Mettl1/SRSF9-dependent alternative splicing provide additional regulatory layers (PMID:19026640, PMID:15657420, PMID:27893713, PMID:30670969, PMID:38810124). NFATc4 functions as a context-dependent survival or apoptotic effector—promoting BDNF-dependent adult hippocampal neurogenesis and spatial memory, yet driving caspase-3-dependent apoptosis in retinal ganglion cells and cochlear hair cells after injury—and is required redundantly with NFATc3 for cardiac development (PMID:22586092, PMID:38639863, PMID:31379853, PMID:12750314).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1999 High

    Established that NFATc4 is a calcium/calcineurin-dependent transcription factor in neurons, resolving how electrical activity is coupled to nuclear gene regulation: L-type calcium channel entry triggers calcineurin-dependent nuclear translocation, while GSK-3 opposes this by phosphorylating NFATc4 to promote export.

    Evidence Live imaging of NFATc4-GFP in hippocampal neurons with pharmacological inhibition of L-type channels, calcineurin inhibitors, and GSK-3 kinase assays

    PMID:10537109

    Open questions at the time
    • Identity of the specific GSK-3 phosphorylation sites on NFATc4 not mapped
    • Downstream neuronal target gene program not characterized genome-wide
  2. 2001 High

    Defined how NFATc4 engages transcriptional coactivators: dual transactivation domains (N- and C-terminal) contact distinct regions of CBP (KIX and CH3 domains), and both contacts are required for transcriptional potentiation.

    Evidence Co-immunoprecipitation with deletion mutagenesis and reporter gene assays

    PMID:11514544

    Open questions at the time
    • Structural basis of dual-domain CBP engagement unknown
    • Whether other NFAT family members share this bipartite mechanism not tested
  3. 2002 High

    Identified Ser168/170 as critical gate-keeping phosphorylation sites: p38 MAPK phosphorylates these residues to enforce cytoplasmic retention, and their mutation to alanine constitutively activates NFATc4, driving PPARγ2 expression and adipocyte differentiation.

    Evidence In vitro kinase assay, site-directed mutagenesis, adipocyte differentiation assays

    PMID:11997522

    Open questions at the time
    • Whether p38 is the dominant kinase at Ser168/170 in all tissues not resolved
  4. 2005 High

    Revealed that ERK/RSK signaling potentiates NFATc4 activity by phosphorylating Ser676, which enhances DNA binding rather than promoting export—establishing a pro-activating kinase input distinct from the export-promoting kinases.

    Evidence DNA affinity isolation, in-gel kinase assay, Ser676 mutagenesis, reporter assays

    PMID:15657420

    Open questions at the time
    • How Ser676 phosphorylation structurally enhances DNA binding is unknown
    • Relative contributions of ERK versus RSK at Ser676 in vivo not quantified
  5. 2005 High

    Expanded NFATc4's cofactor repertoire beyond CBP: NFATc4 interacts with estrogen receptors α and β in a ligand-independent manner, functioning as a coactivator of ER-dependent transcription.

    Evidence Yeast two-hybrid confirmed by Co-IP, in vitro binding, ChIP, and reporter assays

    PMID:16219765

    Open questions at the time
    • ER–NFATc4 target genes in physiological contexts not identified
    • In vivo relevance in estrogen-responsive tissues not demonstrated
  6. 2007 High

    RSK2 was identified as a direct NFATc4 interactor with defined binding domains, showing that RSK2-mediated phosphorylation promotes nuclear localization and drives skeletal muscle differentiation.

    Evidence Co-IP with domain mapping, in vitro kinase assay (Km determined), siRNA knockdown, C2C12 myotube differentiation

    PMID:17213202

    Open questions at the time
    • Whether RSK2 phosphorylates the same Ser676 or additional sites not fully resolved
  7. 2008 High

    Delineated the rephosphorylation cascade at Ser168/170: mTOR maintains basal phosphorylation, while ERK5 rephosphorylates these sites after calcineurin-driven dephosphorylation and primes CK1α-mediated sequential phosphorylation to enforce nuclear export.

    Evidence Phospho-specific antibody, Erk5−/− cells, rapamycin inhibition, in vitro kinase assays

    PMID:18347059

    Open questions at the time
    • Whether additional kinases contribute to Ser168/170 rephosphorylation in specific tissues
  8. 2008 Medium

    Established that GSK-3β not only promotes NFATc4 nuclear export but also targets it for K48-linked polyubiquitination and proteasomal degradation, adding protein turnover as a regulatory layer.

    Evidence Ubiquitination assays with proteasome inhibitors, GSK-3β activation/inhibition, reporter assays

    PMID:19026640

    Open questions at the time
    • The E3 ubiquitin ligase mediating GSK-3β-triggered NFATc4 degradation is unidentified
    • Ubiquitination sites on NFATc4 not mapped
  9. 2009 High

    Demonstrated that NFATc4 functions as a transcriptional repressor at the GAP-43 promoter in neurons and as a survival factor via BDNF promoter IV activation—establishing its dual activator/repressor function depending on target gene context.

    Evidence ChIP in PC-12 cells, cultured neurons, and mouse brain for GAP-43; RNAi knockdown with BDNF rescue for neuronal survival

    PMID:19443652 PMID:19955386

    Open questions at the time
    • Mechanism by which NFATc4 switches between activation and repression at different promoters is unknown
  10. 2010 High

    miR-133a was identified as a direct post-transcriptional repressor of NFATc4 via two conserved sites in its 3′-UTR, providing a microRNA-based mechanism that limits NFATc4 protein levels during cardiac hypertrophy.

    Evidence 3′-UTR luciferase reporter with site-directed mutagenesis, miR-133a gain- and loss-of-function

    PMID:20173049

    Open questions at the time
    • Whether other miRNAs cooperatively regulate NFATc4 not explored
    • In vivo cardiac hypertrophy rescue by miR-133a-mediated NFATc4 suppression not tested
  11. 2010 High

    Lipin 1 was identified as a direct nuclear repressor of NFATc4 transcriptional activity via protein–protein interaction at target gene promoters, revealing a metabolic enzyme as a transcriptional corepressor of NFATc4 in adipocytes.

    Evidence Co-IP, ChIP at target promoters, siRNA knockdown, fld (lipin 1-deficient) mouse tissue

    PMID:20385772

    Open questions at the time
    • Whether lipin 1 enzymatic activity contributes independently from its scaffold function remains debated
  12. 2011 High

    FoxP1 was shown to form a calcineurin-dependent complex with NFATc4 at hypertrophy gene promoters in cardiomyocytes, functioning as a repressive partner that redirects NFATc4 from hypertrophic to homeostatic gene programs.

    Evidence BiFC visualization, mutagenesis at interaction interface, ChIP in neonatal and adult heart tissue

    PMID:21606195

    Open questions at the time
    • How the FoxP1–NFATc4 complex discriminates between hypertrophic and homeostatic promoters
  13. 2011 Medium

    PPARα was found to compete with GATA-4 for NFATc4 binding in cardiomyocytes, suppressing BNP transactivation and hypertrophy—revealing cofactor competition as a mechanism for modulating NFATc4 output.

    Evidence EMSA, Co-IP, PPARα siRNA knockdown, reporter assays in neonatal rat cardiomyocytes

    PMID:22198280

    Open questions at the time
    • Structural basis for PPARα–NFATc4 versus GATA-4–NFATc4 competition is unknown
    • In vivo confirmation in cardiac tissue not provided
  14. 2012 High

    NFATc4 was established as essential for adult hippocampal neurogenesis and spatial memory: BDNF/TrkB-calcineurin-NFATc4 signaling selectively supports survival of adult-born neurons, and NFATc4 knockout impairs LTP and memory.

    Evidence NFATc4−/− mice, stereotaxic cyclosporin A and TrkB-Fc delivery, hippocampal neurogenesis quantification, LTP electrophysiology, behavioral spatial memory testing

    PMID:22586092

    Open questions at the time
    • Downstream transcriptional targets mediating NFATc4-dependent neuronal survival in the adult hippocampus not fully defined
  15. 2012 High

    Clarified isoform-specific activation kinetics: NFATc4 requires prolonged depolarization (1–3 h) for nuclear translocation (unlike rapid NFATc3), the serine-proline repeat region determines activation magnitude, and GSK-3β suppression is specifically required for NFATc4 nuclear import.

    Evidence NFATc3/c4 chimera analysis, live imaging, GSK-3β inhibition, siRNA in hippocampal and DRG neurons

    PMID:22977251

    Open questions at the time
    • Structural basis for how the serine-proline repeat tunes activation threshold is unknown
  16. 2012 High

    NFATc3 and NFATc4 were shown to be redundantly required for cardiac development; double knockout is lethal with defects in myocyte proliferation, trabeculation, and mitochondrial complex II activity, all rescued by constitutively active NFATc4.

    Evidence Genetic double knockout, cardiac-specific transgenic rescue, mitochondrial enzyme assays, electron microscopy

    PMID:12750314

    Open questions at the time
    • Direct transcriptional targets mediating mitochondrial complex II regulation not identified
  17. 2014 High

    Genome-wide ChIP identified GABRA2 and GABRA4 as direct NFATc4 target genes in hippocampal progenitors, linking GABA receptor signaling to calcineurin-NFATc4-dependent adult neurogenesis and anxiety-related behavior.

    Evidence Genome-wide ChIP, luciferase reporters, NFATc4−/− mice, behavioral anxiety tests, pharmacological GABAAR modulation

    PMID:24948817

    Open questions at the time
    • Full set of NFATc4 direct targets in hippocampal progenitors beyond GABRA genes not catalogued
  18. 2016 High

    CDK3 was identified as a direct NFATc4 kinase at Ser259 that enhances transactivation and promotes cell transformation, expanding NFATc4 regulation to cell cycle kinases and oncogenic contexts.

    Evidence Mammalian two-hybrid, in vitro kinase assay, S259A mutagenesis, colony formation, xenograft model

    PMID:27893713

    Open questions at the time
    • Whether CDK3-NFATc4 axis is active in non-transformed cells not established
  19. 2016 High

    NFATc4 was shown to be specifically required (not NFATc2) for neuritin-induced Kv4.2 channel transcription in cerebellar granule neurons, establishing isoform-specific transcriptional control of neuronal excitability.

    Evidence ChIP at Kv4.2 promoter, Nfatc4−/− versus Nfatc2−/− mice, electrophysiology, AAV-neuritin

    PMID:27307045

    Open questions at the time
    • Broader ion channel gene program regulated by NFATc4 in cerebellum not mapped
  20. 2018 Medium

    BDNF was found to sequester NFATc4 in Golgi compartments rather than the nucleus, derepressing an NFI-dependent gene program—revealing a non-canonical extranuclear mechanism of NFATc4 regulation.

    Evidence Subcellular fractionation, Golgi co-localization, gene expression analysis in cerebellar granule cells

    PMID:29467254

    Open questions at the time
    • Mechanism of Golgi retention is unknown
    • Generalizability beyond cerebellar granule cells not tested
  21. 2019 Medium

    SIRT6 deacetylase activity was shown to suppress NFATc4 nuclear accumulation and transcriptional activity in cardiomyocytes, adding lysine acetylation as a regulatory modification controlling NFATc4 localization.

    Evidence Co-IP, deacetylase-dead H133Y mutant, adenoviral overexpression, siRNA knockdown, reporter assays

    PMID:30670969

    Open questions at the time
    • Specific acetylated lysine residues on NFATc4 not identified
    • Whether SIRT6 directly deacetylates NFATc4 or acts indirectly not definitively resolved
  22. 2019 Medium

    NFATc4 deficiency protects cochlear hair cells from ototoxic drug-induced apoptosis via reduced TNF expression, establishing NFATc4 as a pro-apoptotic transcription factor in sensory cells.

    Evidence Nfatc4−/− mice, ototoxic drug treatment, immunofluorescence, hearing function tests

    PMID:31379853

    Open questions at the time
    • Direct binding of NFATc4 to the Tnf promoter in hair cells not demonstrated by ChIP
  23. 2020 High

    NFATc4 was established as a driver of NASH pathogenesis through dual mechanisms: direct binding to and inhibition of PPARα transcriptional activity (impairing fatty acid oxidation) and osteopontin-mediated paracrine activation of macrophages and stellate cells.

    Evidence Co-IP of NFATc4–PPARα, OPN secretion assays, paracrine co-culture, NASH mouse model

    PMID:32717288

    Open questions at the time
    • NFATc4 target genes beyond PPARα and OPN in hepatocytes not catalogued
  24. 2020 High

    NULP1 was identified as a direct NFATc4-interacting repressor whose loss exacerbates cardiac hypertrophy—rescued by NFAT pathway inhibition—adding another nuclear cofactor that restrains NFATc4 output.

    Evidence Co-IP with domain mapping, NULP1 knockout/transgenic mice, VIVIT peptide rescue, aortic banding model

    PMID:32805187

    Open questions at the time
    • Mechanism by which NULP1 inhibits NFATc4 transactivation not resolved
  25. 2021 Medium

    SIRT2-mediated deacetylation was shown to inhibit NFATc4 nuclear translocation in hepatocytes, and NFATc4 represses PPARγ to drive ethanol-induced hepatocyte senescence, linking NFATc4 to alcoholic liver disease.

    Evidence SIRT2 siRNA, NFATc4 overexpression/knockdown, PPARγ epistasis, senescence markers, alcoholic liver mouse model

    PMID:34192554 PMID:34474091

    Open questions at the time
    • Direct deacetylation of NFATc4 by SIRT2 not confirmed by in vitro deacetylation assay
    • NFATc4 acetylation sites remain unmapped
  26. 2023 High

    Phosphoproteomics identified NFATc4 as a calcineurin substrate in adrenal zona glomerulosa cells; NFATc4 directly binds the CYP11B2 promoter and is required for potassium-stimulated aldosterone synthesis, establishing a new physiological role in mineralocorticoid regulation.

    Evidence Phosphoproteomics, ZG-specific CnB1 knockout, NFATc4 knockout, ChIP at CYP11B2 promoter, aldosterone secretion assays

    PMID:37310791

    Open questions at the time
    • Whether NFATc4 cooperates with other transcription factors at CYP11B2 not defined
    • Contribution of NFATc4 to primary aldosteronism not tested
  27. 2024 Medium

    Mettl1-catalyzed m7G modification of SRSF9 mRNA was shown to increase SRSF9, which promotes alternative splicing and stabilization of NFATc4 transcript, activating cardiac hypertrophy—revealing an epitranscriptomic input to NFATc4 regulation.

    Evidence Mettl1 knockout/overexpression, SRSF9 knockdown, alternative splicing analysis, TAC and Ang II mouse models

    PMID:38810124

    Open questions at the time
    • Specific NFATc4 splice variants generated by SRSF9 not characterized
    • Whether this mechanism operates outside the heart is unknown
  28. 2024 High

    NFATc4 (but not NFATc3) knockout was shown to promote retinal ganglion cell survival and delay axonal degeneration after optic nerve crush, with lentiviral re-introduction reversing the protective effect—confirming isoform-specific pro-apoptotic function in the retina via caspase-3.

    Evidence NFATc4−/− and NFATc3−/− mice, optic nerve crush, lentiviral rescue, microarray, caspase-3 immunostaining

    PMID:38639863

    Open questions at the time
    • Direct transcriptional targets of NFATc4 driving RGC apoptosis not identified
    • Whether NFATc4 inhibition is therapeutically viable for glaucoma not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: the identity of the E3 ubiquitin ligase(s) targeting NFATc4, the specific lysine residues subject to acetylation/deacetylation, the structural basis for cofactor selectivity (activator vs. repressor), and the complete genome-wide target gene repertoire across tissues.
  • E3 ligase for NFATc4 ubiquitination unknown
  • Acetylation sites unmapped
  • No structural model of NFATc4 with any cofactor
  • Comprehensive tissue-specific cistrome lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 16 GO:0003677 DNA binding 7
Localization
GO:0005634 nucleus 9 GO:0005829 cytosol 4 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 14 R-HSA-162582 Signal Transduction 8 R-HSA-112316 Neuronal System 5 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1266738 Developmental Biology 1
Partners
CBPESR1FOXP1GATA4GSK3BLPIN1PPARAPPP3CA

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 NFATc4 undergoes calcineurin-dependent nuclear translocation in hippocampal neurons in response to electrical activity or K+ depolarization, specifically requiring calcium entry through L-type voltage-gated calcium channels. GSK-3 phosphorylates NFATc4, promoting its nuclear export and antagonizing NFATc4-dependent transcription. NFATc4 controls expression of the inositol 1,4,5-trisphosphate receptor type 1 gene. Live imaging of NFATc4-GFP translocation in neurons, pharmacological inhibition of L-type channels, GSK-3 kinase assays, calcineurin inhibitor (cyclosporin A/FK506) treatment, reporter gene assays Nature High 10537109
2002 p38 MAP kinase phosphorylates NFATc4 at multiple residues including Ser168 and Ser170 within the NFAT homology domain. Phosphorylation at these sites promotes cytoplasmic retention; Ala168/170 substitutions promote nuclear localization, increase NFAT-mediated transcription, and drive adipocyte differentiation by activating PPARγ2 gene expression via direct NFAT binding elements in the PPARγ2 promoter. In vitro kinase assay, site-directed mutagenesis, stable cell line expression, reporter assays, adipocyte differentiation assays Molecular and cellular biology High 11997522
2001 NFATc4 contains two distinct transactivation domains (N-terminal and C-terminal) that each interact with separate regions of the coactivator CBP (KIX and CH3 domains respectively). Both transactivation domains are required for CBP-mediated potentiation of NFATc4 transcriptional activity; removal of either domain abolishes CBP potentiation. Co-immunoprecipitation, deletion mutagenesis, reporter gene assays The Journal of biological chemistry High 11514544
2005 The ERK/RSK signaling pathway is recruited to the NFATc4-DNA transcription complex. RSK phosphorylates NFATc4 at Ser676, potentiating NFATc4 DNA binding by increasing NFAT-DNA association. ERK also targets Ser676 but interacts with NFATc4 at a distinct region from RSK. DNA affinity isolation, in-gel kinase assay, in vitro phosphorylation, mutagenesis, reporter assays Molecular and cellular biology High 15657420
2007 RSK2 directly interacts with NFATc4 (via N-terminal aa 1-68 and C-terminal aa 416-674 kinase domains of RSK2 binding to aa 261-365 of NFAT3). Upon calcium ionophore stimulation, RSK2 induces nuclear localization of NFATc4 and phosphorylates NFATc4 in vitro (Km = 3.559 µM). RSK2/NFATc4 signaling drives skeletal muscle cell differentiation into multinucleated myotubes. Co-immunoprecipitation, in vitro kinase assay, domain mapping, siRNA knockdown, C2C12 differentiation assay The Journal of biological chemistry High 17213202
2008 mTOR phosphorylates the gate-keeping residues Ser168/170 of NFATc4, maintaining it in the cytoplasm at rest. ERK5 MAP kinase also mediates rephosphorylation of Ser168/170 and promotes NFATc4 nuclear export; ERK5-mediated phosphorylation primes subsequent phosphorylation by CK1α. Ablation of ERK5 in Erk5−/− cells causes defects in NFATc4 rephosphorylation and nucleocytoplasmic shuttling. Phospho-specific monoclonal antibody, kinetic phosphorylation analysis, Erk5−/− cell lines, mTOR inhibition (rapamycin), in vitro kinase assays Molecular and cellular biology High 18347059
2008 GSK-3β promotes NFATc4 ubiquitination through Lys48-linked polyubiquitin chains, decreasing NFATc4 protein levels and transcriptional activity. GSK-3β-induced phosphorylation and ubiquitination represses NFATc4-dependent cardiac gene expression. Ubiquitination assay, proteasome inhibitor treatment, GSK-3β activation/inhibition, reporter assays, Western blot FEBS letters Medium 19026640
2010 Lipin 1 represses NFATc4 transcriptional activity through direct protein-protein interaction and is recruited to NFATc4 target gene promoters in vivo. Catalytically active and inactive lipin 1 both suppress NFATc4, and the suppression may involve recruitment of histone deacetylases. Loss of lipin 1 in adipocytes increases expression of NFATc4 targets including TNFα, resistin, FABP4, and PPARγ. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), reporter assays, siRNA knockdown, lipin 1-deficient (fld) mouse tissue analysis Molecular and cellular biology High 20385772
2012 NFATc4 and NFATc3 form complexes that are required redundantly for cardiac development; NFATc4 constitutively active form rescues ventricular myocyte proliferation, compact zone density, trabecular formation, and cardiac mitochondrial complex II enzymatic activity in nfatc3−/−nfatc4−/− double-knockout embryos. Genetic double knockout, cardiac-specific transgenic rescue, mitochondrial enzyme activity assays, electron microscopy Circulation research High 12750314
2005 NFATc4 (NFAT3) interacts with estrogen receptor alpha and beta in a ligand-independent manner, binding specifically to the AF-1 domain of ERβ. NFATc4 acts as a co-activator of both ERα and ERβ, enhancing their transcriptional activities and increasing NFAT3 binding of ERα to the estrogen-responsive element. Yeast two-hybrid, co-immunoprecipitation in mammalian cells, in vitro binding assay, ChIP, reporter assays, siRNA knockdown The Journal of biological chemistry High 16219765
2011 FoxP1 forms a complex with Nfat3 (NFATc4) in cardiomyocytes, visualized by bimolecular fluorescence complementation (BiFC). Calcineurin activation induces FoxP1-Nfat3 complex formation. FoxP1 represses Nfat3-activated hypertrophy-associated genes (Myh7, Rcan1, Cx43, Anf, Bnp) and activates genes maintaining normal heart function (Myh6, p57Kip2). Co-occupancy of FoxP1 and Nfat3 at hypertrophy gene promoters is demonstrated in vivo. BiFC, amino acid substitution mutagenesis at interaction interface, ChIP in neonatal and adult heart tissue, reporter assays, cardiomyocyte hypertrophy phenotyping Molecular and cellular biology High 21606195
2007 IL-18 induces ERK1/2-dependent phosphorylation of NFATc4 at Ser676, promoting NFATc4 nuclear translocation and in vivo DNA binding to the adiponectin promoter NFAT binding site, thereby suppressing adiponectin transcription in 3T3-L1 adipocytes. Reporter assay with NFAT site mutation, in vivo DNA binding assay, ERK1/2 inhibitors (U0126, PD98059), ERK1/2 siRNA, NFATc4 siRNA knockdown The Journal of biological chemistry High 18086672
2004 NFATc4 (Nishéd-binding partner) forms a ternary complex with the transcription factor Nishéd and co-activator p300 at an intronic regulatory element (IRE) of the MLC-2v gene. Angiotensin II stimulation enhances this complex formation and MLC-2v transcription; losartan (AT1 antagonist) abolishes it. Gel mobility shift assay, co-immunoprecipitation, reporter assays, pharmacological antagonism The Journal of biological chemistry Medium 15272022
2009 NFATc4 is a transcriptional repressor of GAP-43 in neurons. Prior to neurotrophin activation, endogenous NFATc4 occupies the GAP-43 promoter in PC-12 cells, cultured neurons, and mouse brain. Overexpression of NFATc4 represses GAP-43 activation by neurotrophin signaling, and NFATc4 is required to repress GAP-43 and other pro-axon outgrowth genes during specific developmental windows. ChIP in vitro and in vivo, reporter assays, overexpression, promoter in silico analysis validated experimentally The Journal of biological chemistry High 19443652
2009 NFATc4 knockdown induces apoptosis in cortical neurons even under survival conditions. NFATc4 mediates NMDAR-dependent neuronal survival by regulating transcription from BDNF promoter IV; NFATc4 inhibition reduces BDNF expression, and exogenous BDNF rescues the pro-apoptotic effects of NFATc4 inhibition. RNAi knockdown, dominant-negative NFAT expression, reporter assays with BDNF promoter IV, neuronal apoptosis assays The Journal of neuroscience High 19955386
2012 NFATc4 calcineurin-dependent activity is specifically required for survival of adult-born hippocampal neurons in response to BDNF signaling. Cyclosporin A injection or TrkB-Fc (BDNF scavenger) reduces adult-born neuron survival in WT but not NFATc4−/− mice. Loss of NFATc4 leads to selective defects in LTP and spatial memory encoding. NFATc4 knockout mice, stereotaxic drug delivery, calcineurin inhibition, TrkB-Fc scavenger, hippocampal neurogenesis quantification, LTP electrophysiology, spatial memory behavioral testing Proceedings of the National Academy of Sciences High 22586092
2012 NFATc4 activation properties in neurons differ from NFATc3: NFATc4 requires prolonged (1-3 h) depolarization for nuclear translocation whereas NFATc3 translocates rapidly. The serine-proline repeat region of NFATc4 is critical for its activation magnitude. GSK3β suppression is specifically required for NFATc4 nuclear import upon depolarization. NFATc3/NFATc4 chimera analysis, siRNA knockdown, GSK3β inhibition, live imaging of nuclear translocation in hippocampal and DRG neurons, p38 and mTOR inhibition The Journal of biological chemistry High 22977251
2013 NFAT3 directly binds to specific DNA sequences within the BACE1 promoter and activates BACE1 transcription; NFATc4 overexpression increases BACE1 promoter activity, BACE1 protein expression, and Aβ production. ChIP, luciferase reporter assays, overexpression, siRNA knockdown Neurochemical research Medium 25663301
2013 NFAT3 directly regulates miR-140 transcription in OA chondrocytes by binding to the miR-140 regulatory sequence, acting as a transcriptional activator. TGF-β/SMAD3 acts as a repressor. TGF-β interferes with NFAT3 translocation, thereby suppressing miR-140 expression. These roles were established by mutagenesis, ChIP, and siRNA knockdown. ChIP, promoter mutagenesis, siRNA knockdown, immunocytochemistry, reporter assays Arthritis research & therapy High 24257415
2014 NFATc4 drives hippocampal progenitor neurogenesis via the calcineurin/NFATc4 axis. NFATc4 directly regulates GABRA2 and GABRA4 subunit expression by binding to specific promoter responsive elements. GABAAR signaling promotes neurogenesis through NFATc4, and NFATc4-dependent increase in neurogenesis is required for suppression of anxiety response. Genome-wide ChIP, luciferase reporter assays, calcineurin inhibition (cyclosporin A), NFATc4−/− mice, behavioral anxiety testing, pharmacological GABAAR modulation The Journal of neuroscience High 24948817
2016 CDK3 directly interacts with NFATc4 (by mammalian two-hybrid assay) and phosphorylates NFATc4 at Ser259, enhancing its transactivation activity. Mutation of Ser259 to Ala reduces NFATc4-dependent colony formation and xenograft tumor growth. Mammalian two-hybrid assay, in vitro phosphorylation/kinase assay, site-directed mutagenesis (S259A), soft agar colony formation, xenograft mouse model Oncogene High 27893713
2016 NFATc4 is recruited to the Kv4.2 gene promoter and is required for neuritin-induced Kv4.2 transcriptional upregulation. The Ca2+/calcineurin/NFATc4 axis mediates neuritin-induced potentiation of IA densities in cerebellar granule neurons; these effects are absent in Nfatc4−/− but not Nfatc2−/− mice. ChIP, luciferase reporter assays, calcineurin inhibition, Nfatc4−/− mice, electrophysiology, AAV-mediated neuritin overexpression The Journal of biological chemistry High 27307045
2018 BDNF sequesters NFATc4 in extranuclear Golgi compartments, thereby derepressing an NFI-dependent temporal gene program in cerebellar granule cells. This extranuclear sequestration reveals an autoregulatory loop as Bdnf itself is part of the NFI target program. Subcellular fractionation/localization, Golgi co-localization, gene expression analysis, NFATc4 loss-of-function Molecular biology of the cell Medium 29467254
2019 SIRT6, via its deacetylase activity, suppresses NFATc4 expression and activation in cardiomyocytes; SIRT6 interacts with NFATc4, likely facilitating its deacetylation. SIRT6 overexpression elevates NFATc4 phosphorylation, prevents nuclear accumulation, and suppresses transcriptional activity, while deacetylase-dead SIRT6 (H133Y mutant) has no effect. Co-immunoprecipitation, adenoviral overexpression, deacetylase-dead mutant (H133Y), Western blot, immunofluorescence, siRNA knockdown, reporter assays Frontiers in pharmacology Medium 30670969
2019 RCAN1.4 overexpression alleviates liver fibrosis through inhibition of calcineurin/NFAT3 (NFATc4) signaling. Downregulation of RCAN1.4 by DNMT1- and DNMT3b-mediated DNA methylation of its promoter relieves inhibition of calcineurin, activating NFATc4 and promoting HSC activation and fibrogenesis. Bisulfite sequencing PCR, ChIP for DNMT1/DNMT3b, rAAV8-mediated RCAN1.4 overexpression, CaN activity assays, siRNA knockdown, CCl4 mouse fibrosis model Theranostics High 31285763
2020 NFATc4 directly binds to PPARα in the nucleus and negatively regulates its transcriptional activity, impairing hepatic fatty acid oxidation and increasing lipid deposition in NASH. NFATc4 activation also increases osteopontin (OPN) secretion from hepatocytes, driving macrophage-mediated inflammation and hepatic stellate cell fibrosis via paracrine signaling. NFATc4 knockdown (gain/loss of function), co-immunoprecipitation (NFATc4-PPARα), reporter assays, OPN secretion measurement, paracrine co-culture experiments, NASH mouse model Journal of hepatology High 32717288
2020 NULP1 directly interacts with NFATc4 via its topologically associating domain (TAD) through the C-terminal region of NULP1, suppressing NFATc4 transcriptional activity. NULP1 knockout exacerbates cardiac hypertrophy, rescued by NFAT pathway inhibition with VIVIT peptides. Co-immunoprecipitation (domain mapping), NULP1 knockout/transgenic mice, VIVIT peptide treatment, aortic banding model, reporter assays Journal of the American Heart Association High 32805187
2020 NFATc4 nuclear translocation and pathway activation drives quiescence (G0 arrest) and chemotherapy resistance in ovarian cancer cells, in part via downregulation of MYC. Cisplatin treatment triggers NFATc4 nuclear translocation; inhibition of NFATc4 increases chemotherapy response both in vitro and in vivo. NFATc4 overexpression/inhibition, flow cytometry for cell cycle, cisplatin response assays, in vivo xenograft, MYC expression analysis JCI insight Medium 32182216
2021 SIRT2-mediated deacetylation of NFATc4 inhibits its nuclear translocation. In ethanol-exposed hepatocytes, PTS (pterostilbene) rescues SIRT2 expression, which deacetylates NFATc4 and prevents its nuclear translocation; NFATc4 overexpression impairs the ability of PTS to suppress RIPK3 expression and necroptosis. NFATc4 overexpression/knockdown, SIRT2 siRNA knockdown, immunofluorescence for NFATc4 nuclear localization, Western blot for acetylation status, RIPK3 expression Toxicology Medium 34474091
2021 NFATc4 triggers hepatocyte senescence via repression of PPARγ in ethanol-treated hepatocytes. NFATc4 knockdown protected against ethanol-induced senescence markers (SA-β-gal, p16, p21, HMGA1, γH2AX), and PPARγ deficiency abrogated these protective effects. NFATc4 siRNA knockdown, PPARγ knockdown, SA-β-gal staining, Western blot for senescence markers, in vivo mouse alcoholic liver model Toxicology letters Medium 34192554
2022 PPP3CA (calcineurin catalytic subunit) and CAMTA1 competitively bind to NFATc4; CAMTA1 knockdown promotes PPP3CA-mediated dephosphorylation of NFATc4, activating it and promoting colorectal cancer chemoresistance. NFATc4 knockdown reverses chemoresistance caused by CAMTA1 knockdown. Co-immunoprecipitation, NFATc4 knockdown, CAMTA1 overexpression/knockdown, xenograft mouse model, oxaliplatin resistance assays Cell death discovery Medium 35332122
2023 Calcineurin (protein phosphatase 3) dephosphorylates NFATc4 in adrenal zona glomerulosa cells. Phosphoproteomics identified NFATc4 as a calcineurin substrate. ZG-specific deletion of the calcineurin regulatory subunit CnB1 reduces Cyp11b2 expression. NFATc4 directly binds the CYP11B2 (aldosterone synthase) promoter via ChIP, and constitutively active NFATc4 increases CYP11B2 expression; NFATc4 deletion impairs K+-dependent aldosterone synthesis. Phosphoproteomics, ZG-specific CnB1 knockout mice, NFATc4 knockout, constitutively active NFATc4 expression, ChIP for CYP11B2 promoter, aldosterone secretion assays JCI insight High 37310791
2024 Mettl1-catalyzed m7G modification of SRSF9 mRNA increases SRSF9 expression, which then promotes alternative splicing and stabilization of NFATc4, thereby activating cardiac hypertrophy. SRSF9 knockdown protects against TAC- or Mettl1-induced cardiac hypertrophy. YY1 acts as a transcription factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout/overexpression, SRSF9 knockdown, alternative splicing analysis, TAC and Ang II mouse models, m7G modification profiling Advanced science Medium 38810124
2011 PPARα activation by fenofibrate enhances association of PPARα with NFATc4 in the nucleus, competing with and decreasing NFATc4 interaction with GATA-4, thereby reducing transactivation of the BNP gene and inhibiting cardiomyocyte hypertrophy. EMSA, co-immunoprecipitation, PPARα siRNA knockdown, reporter assays, confocal microscopy, primary neonatal rat cardiomyocytes Archives of biochemistry and biophysics Medium 22198280
2016 NFATc4 interacts with myocardin to synergistically activate LTCC α1C (L-type Ca2+ channel) gene expression in ET-1-induced cardiomyocyte hypertrophy. NFATc4 also directly activates myocardin expression by binding to its promoter. Co-immunoprecipitation, ChIP, reporter assays, NFATc4 and myocardin overexpression/knockdown Life sciences Medium 27155398
2017 TBX5 transcription factor binds to the NFAT3 promoter and is required for NFAT3 expression; mutation of the TBX5 binding site in the NFAT3 promoter diminishes promoter activity, while TBX5 overexpression enhances NFAT3 expression. TBX5-mediated NFAT3 expression suppresses IL-2 transcription, establishing TBX5 as a transcriptional regulator of NFAT3 in T cells. NFAT3 suppresses IL-2 promoter activity through its N-terminal transactivation domain, Ca2+-regulatory domain, and DNA-binding domain. Promoter mutagenesis, reporter assays, TBX5 overexpression in CD4+ T cells, siRNA knockdown, chromatin accessibility analysis Journal of immunology Medium 29180489
2019 Orai1-dependent Ca2+ entry activates calcineurin-NFATc4 signaling specifically in endothelial cells; among all NFAT isoforms, TNFα exclusively triggers NFATc4 nuclear accumulation in HUVECs. Orai1 knockdown prevents TNFα-induced NFATc4 nuclear translocation and reduces ICAM-1 and VCAM-1 expression. Orai1 knockdown/overexpression, NFATc4 overexpression, calcineurin inhibition, nuclear translocation imaging, ICAM-1/VCAM-1 expression, in vivo mouse aorta Biochemical and biophysical research communications Medium 29225169
2019 NFATc4 deficiency in cochlear hair cells attenuates ototoxic drug-induced apoptosis. NFATc4 is activated and translocates from cytoplasm to nucleus in response to ototoxic drugs, followed by increased Tnf expression and downstream apoptosis pathway activation. Nfatc4-deficient hair cells show reduced TNF-mediated apoptosis. Nfatc4−/− mice, ototoxic drug treatment, immunofluorescence for NFATc4 localization, Western blot for Tnf and downstream apoptosis markers, hearing function tests Frontiers in immunology Medium 31379853
2024 NFATc4 knockout (but not NFATc3 knockout) increases retinal ganglion cell (RGC) survival, improves retinal function, and delays axonal degeneration after optic nerve crush. NFATc4 up-regulation after injury immunolocalizes to the ganglion cell layer. Lentiviral re-introduction of NFATc4 into NFATc4−/− retinas reverses the pro-survival effect, confirming NFATc4-dependent pro-apoptotic signaling (involving caspase-3). NFATc4−/− and NFATc3−/− mice, optic nerve crush model, lentiviral NFATc4 delivery, microarray, immunostaining for cleaved caspase-3, retinal function assessment Molecular neurobiology High 38639863
2010 miR-133a directly targets two conserved base-pairing sites in the NFATc4 3'-UTR, negatively regulating NFATc4 expression. Mutation of both sites in the NFATc4 3'-UTR completely blocks miR-133a-mediated repression. miR-133a reduces endogenous NFATc4 protein and attenuates hypertrophic stimulus-induced NFATc4 upregulation. Luciferase reporter with 3'-UTR, 3'-UTR site-directed mutagenesis, miR-133a gain-of-function, miR-133a inhibitor treatment, Western blot American journal of physiology. Heart and circulatory physiology High 20173049

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons. Nature 435 10537109
2002 Targeted disruption of NFATc3, but not NFATc4, reveals an intrinsic defect in calcineurin-mediated cardiac hypertrophic growth. Molecular and cellular biology 218 12370307
2002 Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases. Molecular and cellular biology 145 11997522
2003 NFATc3 and NFATc4 are required for cardiac development and mitochondrial function. Circulation research 121 12750314
2004 The transcription factor NFAT3 mediates neuronal survival. The Journal of biological chemistry 102 15537643
2010 Lipin 1 represses NFATc4 transcriptional activity in adipocytes to inhibit secretion of inflammatory factors. Molecular and cellular biology 97 20385772
2000 Electrical stimulation of neonatal cardiac myocytes activates the NFAT3 and GATA4 pathways and up-regulates the adenylosuccinate synthetase 1 gene. The Journal of biological chemistry 94 10636885
2000 Ras regulates NFAT3 activity in cardiac myocytes. The Journal of biological chemistry 89 11044444
2010 NFATc4 is negatively regulated in miR-133a-mediated cardiomyocyte hypertrophic repression. American journal of physiology. Heart and circulatory physiology 83 20173049
2014 Effect of Astragalus polysaccharides on expression of TNF-α, IL-1β and NFATc4 in a rat model of experimental colitis. Cytokine 77 25132256
2007 RSK2 mediates muscle cell differentiation through regulation of NFAT3. The Journal of biological chemistry 64 17213202
2013 NFAT3 and TGF-β/SMAD3 regulate the expression of miR-140 in osteoarthritis. Arthritis research & therapy 61 24257415
2009 Nuclear factor of activated T-cells isoform c4 (NFATc4/NFAT3) as a mediator of antiapoptotic transcription in NMDA receptor-stimulated cortical neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 59 19955386
2005 Stimulatory cross-talk between NFAT3 and estrogen receptor in breast cancer cells. The Journal of biological chemistry 53 16219765
2012 Nuclear factor of activated T cells (NFATc4) is required for BDNF-dependent survival of adult-born neurons and spatial memory formation in the hippocampus. Proceedings of the National Academy of Sciences of the United States of America 50 22586092
2010 NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene. Oncogene 49 20101218
2019 Methylation of RCAN1.4 mediated by DNMT1 and DNMT3b enhances hepatic stellate cell activation and liver fibrogenesis through Calcineurin/NFAT3 signaling. Theranostics 47 31285763
2005 Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex. Molecular and cellular biology 47 15657420
2013 Fenofibrate ameliorates cardiac hypertrophy by activation of peroxisome proliferator-activated receptor-α partly via preventing p65-NFκB binding to NFATc4. Molecular and cellular endocrinology 44 23518069
2008 Deafferentation-induced activation of NFAT (nuclear factor of activated T-cells) in cochlear nucleus neurons during a developmental critical period: a role for NFATc4-dependent apoptosis in the CNS. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 18354019
2020 NFATC4 promotes quiescence and chemotherapy resistance in ovarian cancer. JCI insight 41 32182216
2006 NFAT3 is specifically required for TNF-alpha-induced cyclooxygenase-2 (COX-2) expression and transformation of Cl41 cells. Journal of cell science 41 16803872
2007 T-type Ca2+ channel blockers prevent cardiac cell hypertrophy through an inhibition of calcineurin-NFAT3 activation as well as L-type Ca2+ channel blockers. Life sciences 40 18275974
2008 Integration of protein kinases mTOR and extracellular signal-regulated kinase 5 in regulating nucleocytoplasmic localization of NFATc4. Molecular and cellular biology 39 18347059
2024 The m7G Methyltransferase Mettl1 Drives Cardiac Hypertrophy by Regulating SRSF9-Mediated Splicing of NFATc4. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 38 38810124
2012 Distinct activation properties of the nuclear factor of activated T-cells (NFAT) isoforms NFATc3 and NFATc4 in neurons. The Journal of biological chemistry 37 22977251
2014 Modulation of GABAA receptor signaling increases neurogenesis and suppresses anxiety through NFATc4. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 24948817
2020 Targeting NFATc4 attenuates non-alcoholic steatohepatitis in mice. Journal of hepatology 34 32717288
2009 NFAT-3 is a transcriptional repressor of the growth-associated protein 43 during neuronal maturation. The Journal of biological chemistry 34 19443652
2012 Genetic polymorphisms of the transcription factor NFATc4 and development of new-onset diabetes after transplantation in Hispanic kidney transplant recipients. Transplantation 33 22234350
2019 SIRT6 Suppresses NFATc4 Expression and Activation in Cardiomyocyte Hypertrophy. Frontiers in pharmacology 32 30670969
2011 PPARα activation inhibits endothelin-1-induced cardiomyocyte hypertrophy by prevention of NFATc4 binding to GATA-4. Archives of biochemistry and biophysics 32 22198280
2007 Interleukin-18 suppresses adiponectin expression in 3T3-L1 adipocytes via a novel signal transduction pathway involving ERK1/2-dependent NFATc4 phosphorylation. The Journal of biological chemistry 32 18086672
2016 Neuritin Up-regulates Kv4.2 α-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway. The Journal of biological chemistry 31 27307045
2016 Phosphorylation of NFAT3 by CDK3 induces cell transformation and promotes tumor growth in skin cancer. Oncogene 30 27893713
2011 Opposing roles of FoxP1 and Nfat3 in transcriptional control of cardiomyocyte hypertrophy. Molecular and cellular biology 30 21606195
2019 Lercanidipine boosts the efficacy of mesenchymal stem cell therapy in 3-NP-induced Huntington's disease model rats via modulation of the calcium/calcineurin/NFATc4 and Wnt/β-catenin signalling pathways. Neurochemistry international 28 31539560
2021 Pterostilbene attenuates RIPK3-dependent hepatocyte necroptosis in alcoholic liver disease via SIRT2-mediated NFATc4 deacetylation. Toxicology 27 34474091
2013 Up-regulation of NFATc4 involves in neuronal apoptosis following intracerebral hemorrhage. Cellular and molecular neurobiology 27 23852416
2010 Activation of a nuclear factor of activated T-lymphocyte-3 (NFAT3) by oxidative stress in carboplatin-mediated renal apoptosis. British journal of pharmacology 27 20718735
2015 Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology. Stem cell reports 26 26235896
2008 Repression of NFAT3 transcriptional activity by estrogen receptors. Cellular and molecular life sciences : CMLS 26 18668201
2005 Constrictor-induced translocation of NFAT3 in human and rat pulmonary artery smooth muscle. American journal of physiology. Lung cellular and molecular physiology 24 16055480
2001 Requirement of two NFATc4 transactivation domains for CBP potentiation. The Journal of biological chemistry 24 11514544
2021 NFATc4 mediates ethanol-triggered hepatocyte senescence. Toxicology letters 23 34192554
2018 Controllability in an islet specific regulatory network identifies the transcriptional factor NFATC4, which regulates Type 2 Diabetes associated genes. NPJ systems biology and applications 22 29977601
2009 Doxorubicin-mediated apoptosis in glioma cells requires NFAT3. Cellular and molecular life sciences : CMLS 22 19784808
2006 Involvement of oxidants and AP-1 in angiotensin II-activated NFAT3 transcription factor. American journal of physiology. Cell physiology 21 17108007
2004 A ternary complex of transcription factors, Nishéd and NFATc4, and co-activator p300 bound to an intronic sequence, intronic regulatory element, is pivotal for the up-regulation of myosin light chain-2v gene in cardiac hypertrophy. The Journal of biological chemistry 21 15272022
2014 L-carnitine protects against carboplatin-mediated renal injury: AMPK- and PPARα-dependent inactivation of NFAT3. PloS one 20 25090113
2015 KMUP-1 Attenuates Endothelin-1-Induced Cardiomyocyte Hypertrophy through Activation of Heme Oxygenase-1 and Suppression of the Akt/GSK-3β, Calcineurin/NFATc4 and RhoA/ROCK Pathways. Molecules (Basel, Switzerland) 19 26056815
2007 Direct evidence for the critical role of NFAT3 in benzo[a]pyrene diol-epoxide-induced cell transformation through mediation of inflammatory cytokine TNF induction in mouse epidermal Cl41 cells. Carcinogenesis 19 17522069
2005 Immunolocalization of NFATc4 in the adult mouse brain. Journal of neuroscience research 18 16273547
2017 Downregulation of NFAT3 Due to Lack of T-Box Transcription Factor TBX5 Is Crucial for Cytokine Expression in T Cells. Journal of immunology (Baltimore, Md. : 1950) 17 29180489
2014 Interleukin-13-induced MUC5AC expression is regulated by a PI3K-NFAT3 pathway in mouse tracheal epithelial cells. Biochemical and biophysical research communications 17 24583134
2017 Inhibition of Orai1-mediated Ca2+ entry limits endothelial cell inflammation by suppressing calcineurin-NFATc4 signaling pathway. Biochemical and biophysical research communications 16 29225169
2012 Dopamine D1 receptors regulate type 1 inositol 1,4,5-trisphosphate receptor expression via both AP-1- and NFATc4-mediated transcriptional processes. Journal of neurochemistry 16 22686291
2019 Nfatc4 Deficiency Attenuates Ototoxicity by Suppressing Tnf-Mediated Hair Cell Apoptosis in the Mouse Cochlea. Frontiers in immunology 15 31379853
2013 Regulation of type 1 IP₃ receptor expression by dopamine D2-like receptors via AP-1 and NFATc4 activation. Neuropharmacology 15 23597509
2010 BNIP3 induces IL6 and calcineurin/NFAT3 hypertrophic-related pathways in H9c2 cardiomyoblast cells. Molecular and cellular biochemistry 15 20852920
2008 Regulation of the stability and transcriptional activity of NFATc4 by ubiquitination. FEBS letters 15 19026640
2006 Knockdown of NFAT3 blocked TPA-induced COX-2 and iNOS expression, and enhanced cell transformation in Cl41 cells. Journal of cellular biochemistry 15 16475165
2018 BDNF activates an NFI-dependent neurodevelopmental timing program by sequestering NFATc4. Molecular biology of the cell 14 29467254
2015 Transcriptional regulation of BACE1 by NFAT3 leads to enhanced amyloidogenic processing. Neurochemical research 14 25663301
2020 Extracellular vesicles produced by NFAT3-expressing cells hinder tumor growth and metastatic dissemination. Scientific reports 13 32488182
2020 NULP1 Alleviates Cardiac Hypertrophy by Suppressing NFAT3 Transcriptional Activity. Journal of the American Heart Association 13 32805187
2013 Spatiotemporal changes in NFATc4 expression of retinal ganglion cells after light-induced damage. Journal of molecular neuroscience : MN 13 24362677
2017 Distinct roles of NFATc1 and NFATc4 in human primary myoblast differentiation and in the maintenance of reserve cells. Journal of cell science 12 28760926
2017 NFAT3/c4-mediated excitotoxicity in hippocampal apoptosis during radiation-induced brain injury. Journal of radiation research 12 28992110
2016 NFATc4 and myocardin synergistically up-regulate the expression of LTCC α1C in ET-1-induced cardiomyocyte hypertrophy. Life sciences 12 27155398
2023 Calcineurin regulates aldosterone production via dephosphorylation of NFATC4. JCI insight 11 37310791
2014 Increased expression of NF-AT3 and NF-AT4 in the atria correlates with procollagen I carboxyl terminal peptide and TGF-β1 levels in serum of patients with atrial fibrillation. BMC cardiovascular disorders 11 25422138
2019 Inhibition of calcineurin/NFATc4 signaling attenuates ventilator‑induced lung injury. Molecular medicine reports 10 31789412
2014 NFAT1 and NFAT3 cooperate with HDAC4 during regulation of alternative splicing of PMCA isoforms in PC12 cells. PloS one 10 24905014
2017 Lercanidipine attenuates angiotensin II-induced cardiomyocyte hypertrophy by blocking calcineurin-NFAT3 and CaMKII-HDAC4 signaling. Molecular medicine reports 9 28849081
2017 The effect of brain-derived neurotrophic factor on radiation-induced neuron architecture impairment is associated with the NFATc4/3 pathway. Brain research 9 29288061
2015 Na(+)/H (+) exchanger isoform 1 induced osteopontin expression in cardiomyocytes involves NFAT3/Gata4. Molecular and cellular biochemistry 9 25758355
2014 Novel role for NFAT3 in ERK-mediated regulation of CXCR4. PloS one 9 25514788
2006 Tissue type-specific modulation of ER transcriptional activity by NFAT3. Biochemical and biophysical research communications 9 17194453
2018 The group VIA calcium-independent phospholipase A2 and NFATc4 pathway mediates IL-1β-induced expression of chemokines CCL2 and CXCL10 in rat fibroblasts. The FEBS journal 8 29637744
2017 17β-Estradiol and/or estrogen receptor alpha blocks isoproterenol-induced calcium accumulation and hypertrophy via GSK3β/PP2A/NFAT3/ANP pathway. Molecular and cellular biochemistry 8 28577190
2024 NFATc4 Knockout Promotes Neuroprotection and Retinal Ganglion Cell Regeneration After Optic Nerve Injury. Molecular neurobiology 7 38639863
2018 Short-Term Treatment with Esmolol Reverses Left Ventricular Hypertrophy in Adult Spontaneously Hypertensive Rats via Inhibition of Akt/NF-κB and NFATc4. BioMed research international 7 29670896
2010 Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway. Molecular medicine reports 7 21472269
2020 Cardiac CaMKIIδ and Wenxin Keli Prevents Ang II-Induced Cardiomyocyte Hypertrophy by Modulating CnA-NFATc4 and Inflammatory Signaling Pathways in H9c2 Cells. Evidence-based complementary and alternative medicine : eCAM 6 33149757
2018 [Effects of hydrogen sulfide (H2S) on cardiac hypertrophy and miRNA-133a-mediated Ca2+/calcineurin/NFATc4 signal pathway in rats]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 6 29926655
2011 Capillary electrophoretic mobility shift assay for binding of DNA with NFAT3, a transcription factor from H9c2 cardiac myoblast cells. Electrophoresis 6 21792994
2022 CAMTA1-PPP3CA-NFATc4 multi-protein complex mediates the resistance of colorectal cancer to oxaliplatin. Cell death discovery 5 35332122
2019 Involvement of calcineurin/NFATc4 pathway in a single-prolonged stress-based rat model of post-traumatic stress disorder. Molecular biology reports 5 31486013
2006 Involvement of nuclear factor of activated T cells 3 (NFAT3) in cyclin D1 induction by B[a]PDE or B[a]PDE and ionizing radiation in mouse epidermal Cl 41 cells. Molecular and cellular biochemistry 4 16645724
2006 NFAT3 is required for EGF-induced COX-2 transcription, but neither iNOS transcription nor cell transformation in Cl 41 cells. Molecular and cellular biochemistry 4 16718377
2023 How does NFAT3 regulate the occurrence of cardiac hypertrophy? International journal of cardiology. Heart & vasculature 3 37753338
2020 Inhibition of the NFATc4/ERK/AKT Pathway and Improvement of Thiol-Specific Oxidative Stress by Dronedarone Possibly Secondary to the Reduction of Blood Pressure in an Animal Model of Ventricular Hypertrophy. Frontiers in physiology 3 32982770
2013 p85α mediates NFAT3-dependent VEGF induction in the cellular UVB response. Journal of cell science 3 23390317
2010 [Expression and significance of COX-2 and its transcription factors NFAT3 and c-Jun in non-small cell lung cancer]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 3 21081043
2025 Multi-parameter magnetic resonance imaging of zebularine in liver fibrosis treatment and calcineurin/NFAT3 mechanism. World journal of gastroenterology 2 40495950
2025 Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4. Journal of ginseng research 2 40843009
2024 NFAT3-FasL axis synchronously regulates apoptosis and necroptosis in murine cochlear outer hair cells after noise trauma. Frontiers in molecular neuroscience 2 39077755
2023 4'‑O‑methylbavachalcone inhibits succinate induced cardiomyocyte hypertrophy via the NFATc4 pathway. Experimental and therapeutic medicine 2 37006873
2004 [CaN-NFAT3 signal pathway: a crucial hinge relates Ca2+ signal with cardiomyocyte hypertrophy]. Zhonghua nei ke za zhi 2 14990015