Affinage

NFATC1

Nuclear factor of activated T-cells, cytoplasmic 1 · UniProt O95644

Length
943 aa
Mass
101.2 kDa
Annotated
2026-04-29
100 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFATc1 is a calcium/calcineurin-regulated transcription factor that integrates signal-dependent dephosphorylation with multi-kinase rephosphorylation to control gene expression across diverse developmental and homeostatic programs. Calcineurin dephosphorylates conserved serine residues to drive nuclear import and DNA binding, while GSK-3, JNK, ERK, p38, CK2, and DYRK1A phosphorylate overlapping or adjacent sites to promote nuclear export, inhibit DNA binding, or modulate protein stability (PMID:9072970, PMID:10652349, PMID:11063740, PMID:28235034). NFATc1 functions as the master transcriptional switch for osteoclastogenesis—induced by RANKL/TRAF6/c-Fos signaling and sustained by autoregulation of its own P1 promoter—where it cooperates with PU.1, MITF, STAT3, and AP-1 to activate target genes including cathepsin K, OSCAR, CCR1, and SLC7A11 (PMID:12479813, PMID:16275763, PMID:17403683, PMID:31462535). Beyond bone, NFATc1 is essential for cardiac valve morphogenesis through calcineurin-dependent nuclear entry in endocardial cells, maintains hair follicle stem cell quiescence by repressing CDK4, drives B-1a cell development, regulates PD-1 expression in T cells, and—when SUMOylated—represses IL-2 to shape regulatory T cell responses (PMID:9515964, PMID:18243104, PMID:14595020, PMID:18802087, PMID:32986812).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 High

    Identifying the kinase that opposes calcineurin-mediated NFATc1 activation revealed that GSK-3 directly phosphorylates conserved N-terminal serines to drive nuclear export, establishing the core phosphorylation/dephosphorylation toggle governing NFATc1 subcellular localization.

    Evidence Biochemical purification of NFATc1 kinase activity followed by in vitro phosphorylation and nuclear localization assays

    PMID:9072970

    Open questions at the time
    • Identity of the GSK-3 priming kinase was not resolved
    • In vivo significance of GSK-3-mediated export not tested
  2. 1998 High

    Genetic knockout and structural studies simultaneously revealed that NFATc1 is essential for cardiac valve formation—acting through calcineurin-dependent nuclear translocation in endocardial cells—and that its DNA-binding domain undergoes conformational reorientation upon cooperative complex formation with AP-1.

    Evidence NFATc1 knockout mice showing lethal valve defects with cyclosporin A phenocopy; NMR solution structure of NFATc1 DBD–DNA complex

    PMID:9506523 PMID:9515964

    Open questions at the time
    • Downstream transcriptional targets in endocardial cells were not identified
    • Structural basis of full-length NFATc1 regulation by phosphorylation remained unknown
  3. 2000 High

    Expanding the kinase network controlling NFATc1 showed that JNK, ERK, p38, and CK2 each physically associate with and phosphorylate the N-terminal regulatory domain to block nuclear import, while GSK-3 phosphorylation was further shown to directly inhibit DNA-binding activity—not just localization.

    Evidence Co-immunoprecipitation and in vitro kinase assays with localization readouts; EMSA with GSK-3-phosphorylated NFATc1 and Ser-Pro repeat mutants

    PMID:10652349 PMID:11063740

    Open questions at the time
    • Relative contributions of individual kinases in physiological contexts undetermined
    • Whether all kinases act simultaneously or in sequence was not addressed
  4. 2001 High

    Demonstrating pattern-specific nuclear translocation in adult muscle fibers established that NFATc1 decodes calcium signaling frequency, translocating only in response to slow-twitch stimulation patterns to control fiber-type gene expression.

    Evidence GFP-NFATc1 live imaging in electrically stimulated adult mouse skeletal muscle fibers with cyclosporin A validation

    PMID:11581284

    Open questions at the time
    • Direct transcriptional targets in slow-twitch fibers not identified
    • Mechanism discriminating stimulation frequencies upstream of calcineurin unclear
  5. 2002 High

    The discovery that RANKL induces NFATc1 via TRAF6/c-Fos and Ca²⁺ oscillation–calcineurin signaling, and that NFATc1-deficient cells cannot form osteoclasts while ectopic NFATc1 suffices, established NFATc1 as the master transcription factor for osteoclastogenesis. Concurrently, autoregulation of the P1 promoter by the short NFATc1/αA isoform was identified in T cells.

    Evidence NFATc1−/− ES cell differentiation, retroviral ectopic expression bypassing RANKL, Ca²⁺ oscillation imaging; P1 promoter reporter dissection and isoform-specific expression analysis

    PMID:12121669 PMID:12479813

    Open questions at the time
    • The full set of NFATc1 osteoclast target genes was not defined
    • Isoform-specific functions beyond apoptosis resistance remained unexplored
  6. 2003 High

    Establishing a cell-intrinsic requirement for NFATc1—but not NFATc2—in B-1a cell development demonstrated non-redundant roles of NFAT family members in lymphocyte lineage commitment.

    Evidence NFATc1−/− and NFATc2−/− mice, mixed-allotype chimeras, retroviral rescue, flow cytometry

    PMID:14595020

    Open questions at the time
    • Downstream target genes in B-1a cells not identified
    • Mechanism of selective NFATc1 elevation in B-1a cells unknown
  7. 2005 High

    Demonstrating that NFATc1 autoregulates its own P1 promoter via tandem NFAT sites within a CpG island explained the sustained high expression unique to committed osteoclasts, and the inability of NFATc2 to substitute in vivo despite in vitro rescue capacity. Concurrently, CCR1 was identified as a direct NFATc1 target controlling osteoclast precursor migration.

    Evidence Adoptive transfer of NFATc1−/− HSCs, blastocyst complementation, ChIP/reporter for P1 autoregulation; CCR1 promoter reporter with cyclosporin A suppression and siRNA migration assay

    PMID:16275763 PMID:16355273

    Open questions at the time
    • Epigenetic mechanism maintaining P1 CpG island accessibility not fully defined
    • Whether CCR1 regulation requires NFATc1 co-factors was not tested
  8. 2007 High

    ChIP at osteoclast target gene promoters revealed a sequential assembly model: MITF/PU.1 complexes pre-occupy promoters in response to CSF-1, RANKL adds p38-phosphorylated MITF and SWI/SNF, and NFATc1 is recruited last during terminal differentiation to sustain expression.

    Evidence ChIP at cathepsin K and ACP5 promoters, Co-IP of MITF/PU.1 complexes, MITF/PU.1 mouse models

    PMID:17403683

    Open questions at the time
    • Order of factor departure from promoter upon signal withdrawal unknown
    • Whether SWI/SNF recruitment depends on NFATc1 not tested
  9. 2008 High

    Two non-overlapping roles were established: NFATc1 directly activates PD-1 transcription in T cells by binding a novel regulatory element at the pdcd1 locus, and NFATc1 maintains hair follicle stem cell quiescence by repressing CDK4 downstream of BMP signaling.

    Evidence ChIP and binding-site mutagenesis at the pdcd1 locus with reporter assay; conditional NFATc1 ablation in skin with CDK4 reporter analysis

    PMID:18243104 PMID:18802087

    Open questions at the time
    • Co-factors mediating NFATc1 repression of CDK4 not identified
    • Whether NFATc1 regulates other immune checkpoint genes was not explored
  10. 2009 Medium

    FOXP3 was shown to compete with NFAT1 for binding at the NFATc1 promoter to suppress its transcription in Tregs, revealing a mechanism for Treg anergy; separately, VEGF and RANKL were found to activate NFATc1 through distinct co-signaling pathways (MEK/ERK vs. JNK) to control endocardial cushion cell proliferation versus cathepsin K induction during valve development.

    Evidence ChIP competition of FOXP3/NFAT1 at NFATc1 promoter, retroviral rescue of IL-2; NFATc1−/− mice plus chick ECC explants with pharmacological MEK/JNK/calcineurin inhibition

    PMID:19564342 PMID:19661463

    Open questions at the time
    • Whether FOXP3-NFATc1 promoter competition occurs genome-wide is unknown
    • Quantitative contributions of MEK vs. JNK pathways in vivo not resolved
  11. 2011 High

    DYRK1A was identified as an NFATc1 kinase in osteoclasts (opposed by harmine inhibition), and NFATc1 was found to play a non-osteoclast role in epicardium-derived cells where RANKL/NFATc1 induces cathepsin K for extracellular matrix invasion during coronary vessel development.

    Evidence In vitro DYRK1A phosphorylation assay with harmine inhibition in RAW264.7 cells; conditional NFATc1 knockout in EPDCs with in vivo embryonic analysis

    PMID:21447555 PMID:21504804

    Open questions at the time
    • Specific DYRK1A phosphorylation sites on NFATc1 were not mapped in this study
    • Other NFATc1 target genes in EPDCs beyond cathepsin K not explored
  12. 2014 High

    NFATc1 was shown to form a transcriptional complex with STAT3 that drives oncogenic enhancer-promoter communications in Kras-driven pancreatic carcinogenesis; separately, STAT3 was identified as a direct transcriptional activator of the NFATc1 promoter in osteoclasts, and NFATc1 was found to create a positive feedback loop by directly activating Itpr2 transcription in cardiomyocytes.

    Evidence Co-IP of NFATc1-STAT3, ChIP in pancreatic cancer GEMMs; conditional Stat3 KO with ChIP at NFATc1 promoter and rescue; ChIP at Itpr2 promoter in calcineurin-A transgenic mice

    PMID:24415751 PMID:24694735 PMID:31462535

    Open questions at the time
    • Full genome-wide NFATc1-STAT3 co-occupancy map not generated
    • Whether Itpr2 feedback is specific to pathological hypertrophy or operates in normal physiology unclear
  13. 2015 High

    NFATc1 was found to cooperate with Sox2 to drive EMT and cancer stemness in pancreatic cancer, opposed by p53-miR200c, and PU.1 was shown to directly transactivate the NFATc1 promoter in osteoclasts.

    Evidence Co-IP of NFATc1-Sox2 in GEMM pancreatic cancer cells with EMT assays; ChIP for PU.1 at NFATc1 promoter with siRNA/retroviral rescue

    PMID:25586376 PMID:26117255

    Open questions at the time
    • NFATc1-Sox2 direct versus indirect DNA co-binding not distinguished
    • Whether PU.1 transactivation of NFATc1 is independent of autoregulatory loop not tested
  14. 2017 High

    DYRK1A was shown to phosphorylate specific NFATc1/αA residues (S261, S278, S403, S409) that paradoxically stabilize the protein by blocking ubiquitin-proteasome degradation, contrasting its destabilizing effect on NFATc2; separately, Gα13-RhoA-Akt-GSK3β signaling was identified as a negative regulator of NFATc1 in osteoclasts.

    Evidence In vitro phosphorylation with site-specific mutants and ubiquitination assay; osteoclast-lineage Gna13 conditional KO with pharmacological epistasis

    PMID:28102206 PMID:28235034

    Open questions at the time
    • Structural basis for divergent DYRK1A effects on NFATc1 vs. NFATc2 stability unknown
    • Whether Gα13 pathway operates in non-bone contexts not explored
  15. 2018 High

    Epigenetic regulation at the NFATc1 locus was established through ASXL1 loss, which reduces H3K27me3 and increases H3K4me3 at the NFATc1 promoter via Jmjd3 histone demethylase, explaining enhanced NFATc1 expression and osteoclastogenesis in ASXL1-deficient cells.

    Evidence Conditional ASXL1 KO in myeloid cells, ChIP for H3K27me3/H3K4me3 at NFATc1 promoter, Jmjd3 siRNA rescue

    PMID:30266822

    Open questions at the time
    • Whether ASXL1-dependent epigenetic regulation of NFATc1 occurs outside the myeloid lineage unknown
    • Full set of Jmjd3-regulated loci beyond NFATc1 not defined
  16. 2019 Medium

    Homer2/3 scaffold proteins were identified as Ca²⁺-independent modulators that physically interact with NFATc1 and gate its access to calcineurin; RANKL disrupts the Homer–NFATc1 interaction to enable dephosphorylation and nuclear translocation.

    Evidence Homer2/3 double KO mice, Co-IP of Homer with NFATc1 and calcineurin, Ca²⁺ oscillation measurements showing no change, cyclosporin A rescue

    PMID:31319381

    Open questions at the time
    • Structural basis of Homer–NFATc1 interaction not determined
    • Whether Homer regulation applies to non-osteoclast contexts unknown
  17. 2021 High

    SUMOylation of NFATc1 was shown to function as a post-translational switch that represses IL-2 production; preventing SUMOylation in knock-in mice elevated IL-2, expanded Tregs via STAT5/Blimp-1, and suppressed autoimmune and alloreactive responses.

    Evidence Transgenic knock-in mouse with prevented NFATc1 SUMO modification, EAE and GVHD disease models, cytokine and signaling analysis

    PMID:32986812

    Open questions at the time
    • SUMO site(s) on NFATc1 and the E3 SUMO ligase were not identified in this study
    • Whether SUMOylation affects NFATc1 function outside T cells not addressed
  18. 2022 High

    NFATc1 was linked to hepatic ER stress: hepatocyte-specific depletion prevents NAFLD progression by blocking PERK-CHOP UPR and NLRP3 inflammasome activation, revealing a metabolic-inflammatory role beyond its canonical immune and bone functions.

    Evidence Hepatocyte-specific NFATc1 conditional KO and overexpression transgenic mice on high-fat diet, PERK-CHOP and NLRP3 pathway analysis

    PMID:35365570

    Open questions at the time
    • Whether NFATc1 directly binds PERK or CHOP gene promoters not tested
    • Upstream signals activating NFATc1 in hepatocyte ER stress not defined
  19. 2024 High

    Metabolic control of NFATc1 expression was established: the serine synthesis pathway generates α-ketoglutarate that fuels histone demethylases removing H3K27me3 from the Nfatc1 locus, coupling amino acid metabolism to osteoclast maturation through epigenetic derepression.

    Evidence Conditional PHGDH KO in osteoclast progenitors, ChIP for H3K27me3 at Nfatc1 locus, α-ketoglutarate supplementation rescue

    PMID:38200114

    Open questions at the time
    • Identity of the specific demethylase(s) acting at the Nfatc1 locus downstream of α-ketoglutarate not determined
    • Whether this metabolic-epigenetic axis regulates NFATc1 in non-osteoclast lineages unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive characterization of individual kinases, co-factors, and epigenetic inputs, the integrated quantitative logic by which NFATc1 integrates simultaneous phosphorylation by multiple kinases, SUMOylation, and epigenetic accessibility to produce tissue-specific transcriptional outputs remains undefined; no full-length structural model of NFATc1 in complex with calcineurin exists.
  • No full-length NFATc1 structure or NFATc1–calcineurin co-structure available
  • Quantitative model of combinatorial post-translational modification integration lacking
  • Genome-wide map of NFATc1 occupancy across multiple cell types not generated in these studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 7 GO:0005829 cytosol 3
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-4839726 Chromatin organization 2
Partners
DYRK1AGSK3BHOMER2HOMER3MITFSOX2SPI1STAT3
Complex memberships
NFATc1-AP-1NFATc1-STAT3NFATc1-Sox2NFATc1-calcineurin

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 RANKL selectively induces NFATc1 expression via TRAF6 and c-Fos signaling pathways, and RANKL-evoked Ca2+ oscillations lead to calcineurin-mediated activation (dephosphorylation) of NFATc1, triggering a sustained NFATc1-dependent transcriptional program during osteoclast differentiation. NFATc1-deficient embryonic stem cells fail to differentiate into osteoclasts, and ectopic NFATc1 expression drives osteoclastogenesis without RANKL, establishing NFATc1 as the master transcriptional switch downstream of RANKL. Genetic knockout (NFATc1-/- ES cells), retroviral ectopic expression, Ca2+ oscillation imaging, calcineurin inhibitor studies Developmental Cell High 12479813
1997 Glycogen synthase kinase-3 (GSK-3) phosphorylates conserved serine residues in the N-terminus of NFATc1, promoting nuclear export and opposing Ca2+-calcineurin-mediated nuclear import. GSK-3 was purified as the NFATc1 kinase (together with a priming kinase activity) and shown to directly phosphorylate NFATc1 conserved serines required for nuclear export. Biochemical purification of NFATc1 kinase activity, in vitro phosphorylation assay, nuclear localization studies Science High 9072970
1998 NFATc1 is essential for cardiac valve formation (aortic and pulmonary valves); it is expressed specifically in cardiac endothelial cells and its nuclear translocation in endocardial cells is controlled by calcineurin, as demonstrated by cyclosporin A treatment retaining NFATc1 in the cytoplasm of normal embryos. Targeted gene disruption (knockout mice), calcineurin inhibitor (cyclosporin A) treatment, immunolocalization in cardiac endothelial cells Nature High 9515964
1998 Solution NMR structure of the binary NFATC1 DNA-binding domain (DBD) complexed with the ARRE2 DNA site from the IL-2 promoter reveals that DNA binding induces folding of structural elements required for sequence-specific recognition and cooperative protein-protein contacts; the orientation of NFAT DBD in the binary complex differs from that in the ternary NFATC2/AP-1/DNA complex, indicating domain reorientation upon formation of a cooperative transcriptional complex. NMR solution structure determination Cell High 9506523
2000 GSK-3 inhibits the intrinsic DNA-binding activity of NFATc1 by phosphorylating the conserved Ser-Pro repeat motifs; calcineurin dephosphorylation enhances DNA binding, while in vitro phosphorylation of NFATc1 by GSK-3 inhibits its ability to bind DNA, demonstrating regulation at the level of DNA-binding activity in addition to subcellular localization. Gel mobility shift assay (EMSA), in vitro phosphorylation, calcineurin activation in cells, NFATc1 Ser-Pro repeat mutant analysis Journal of Biological Chemistry High 11063740
2000 JNK, ERK, p38, and CK2 physically associate with the NFATc1 N-terminal regulatory domain, directly phosphorylate Ser172 and the conserved Ser-Pro repeats to regulate nuclear localization, and overexpression of JNK, ERK, or p38 blocks ionomycin-induced NFATc1 nuclear translocation. CK2 also binds the N-terminus and phosphorylates a conserved motif downstream of Ser-Pro repeats important for nuclear export. Co-immunoprecipitation, in vitro kinase assays, subcellular localization studies, overexpression and pharmacological inhibition of kinases Journal of Biological Chemistry High 10652349
2005 NFATc1 autoregulates its own expression through its P1 promoter (within a CpG island): NFATc1 binds tandemly arranged NFAT sites in its own promoter to sustain high-level expression selectively in osteoclasts in vivo. This autoregulatory loop explains why NFATc2 can rescue osteoclastogenesis in vitro but not in vivo, since NFATc1 autoregulation at the epigenetic level is uniquely required for cell-lineage commitment. Adoptive transfer of NFATc1-/- hematopoietic stem cells, blastocyst complementation, retroviral rescue, promoter analysis (ChIP, reporter assays), NFATc1 ectopic expression Journal of Experimental Medicine High 16275763
2001 NFATc1 undergoes activity-dependent, calcineurin-sensitive nuclear translocation in adult skeletal muscle fibers specifically in response to slow-twitch (10 Hz continuous or 10 Hz trains) but not fast-twitch stimulation patterns, contributing to slow-twitch fiber type-specific gene expression. Constitutively active NFATc1(S→A) shows a distinct intranuclear foci pattern in unstimulated fibers. GFP-fusion protein live imaging in cultured adult mouse skeletal muscle fibers, electrical stimulation with defined patterns, cyclosporin A (calcineurin inhibitor) treatment Journal of Cell Biology High 11581284
2002 The short isoform NFATc1/αA is selectively induced to high levels via autoregulation of the NFATc1 P1 promoter (containing tandem NFAT binding sites within a CpG island DNase I hypersensitive site) by NFATs in effector T cells. This isoform does not promote apoptosis (unlike other NFATs), enhancing effector T cell survival. A second promoter P2 before exon 2 is not NFAT-controlled and directs longer isoforms. Promoter reporter assay, DNase I hypersensitivity mapping, NFAT binding site mutation, apoptosis assays, isoform-specific expression analysis Immunity High 12121669
2008 NFATc1 is preferentially expressed in hair follicle stem cells in their niche where it acts downstream of BMP signaling to transcriptionally repress CDK4 and maintain stem cell quiescence. Pharmacological or genetic NFATc1 ablation leads to premature stem cell activation and precocious follicular growth. Conditional and complete NFATc1 gene ablation, cyclosporin A pharmacological suppression, CDK4 reporter assays, hair follicle stem cell analysis Cell High 18243104
2008 NFATc1 directly binds to a novel regulatory element at the pdcd1 (PD-1) locus to regulate PD-1 gene expression upon T cell activation; NFATc1 binding was demonstrated by ChIP assay, and mutation of the NFATc1 binding site completely abolished promoter activity. Chromatin immunoprecipitation (ChIP), luciferase reporter assay with NFATc1 binding site mutation, calcineurin inhibitor (cyclosporin A) and NFAT inhibitor treatment Journal of Immunology High 18802087
2007 During osteoclast differentiation, MITF and PU.1 form complexes at osteoclast target gene promoters (cathepsin K, acid phosphatase 5) in response to CSF-1 alone, while RANKL+CSF-1 additionally recruit p38 MAPK-phosphorylated MITF and SWI/SNF chromatin-remodeling complexes. NFATc1 is subsequently recruited to these promoter complexes during terminal differentiation to maintain target gene expression. ChIP on target gene promoters, Co-IP of transcription factor complexes, MITF/PU.1 mouse genetic models Journal of Biological Chemistry High 17403683
2014 NFATc1 forms a transcriptional complex with STAT3 in pancreatic epithelial cells that promotes KrasG12D-driven carcinogenesis; NFATc1-STAT3 complexes mediate enhancer-promoter communications at jointly regulated oncogenic genes (Cyclin, EGFR, WNT family members). Genetic or pharmacologic NFATc1 ablation attenuates inflammation-induced carcinogenesis. Co-immunoprecipitation, ChIP, genetic mouse models (NFATc1 activation/ablation in KrasG12D background), pharmacological inhibition Cancer Discovery High 24694735
2011 RANKL/NFATc1 signaling in epicardium-derived cells (EPDCs) induces cathepsin K (CTSK) expression for extracellular matrix degradation and cell invasion into myocardium; conditional loss of NFATc1 in EPDCs reduces coronary vessel and fibrous matrix penetration. RANKL treatment induces Ctsk expression in PE-derived cell cultures via a calcineurin-dependent mechanism. Conditional knockout of NFATc1 in EPDCs, calcineurin inhibitor treatment, RANKL stimulation of PE-derived cell cultures, in vivo embryonic analysis Development High 21447555
2014 STAT3 drives the transcription of NFATc1 by directly binding to its promoter in osteoclasts; STAT3-deficient bone marrow macrophages show decreased NFATc1 expression and impaired osteoclast differentiation, which is rescued by enforced NFATc1 expression. Conditional Stat3 knockout (Ctsk-Cre), ChIP for STAT3 binding to NFATc1 promoter, siRNA knockdown of STAT3, enforced NFATc1 expression rescue Journal of Biological Chemistry High 31462535
2017 DYRK1A phosphorylates NFATc1/αA at S261, S278, S403, and S409, interfering with NFATc1 ubiquitination and ubiquitin-proteasome degradation, thereby increasing NFATc1 protein stability and transcriptional activity (in contrast to its known role in destabilizing NFATc2). In vitro phosphorylation assay with site-specific mutants, ubiquitination assay, protein stability analysis PLoS ONE High 28235034
2011 DYRK1A directly inhibits NFATc1 through phosphorylation (inactivation); harmine, a DYRK1A inhibitor, promotes NFATc1 dephosphorylation/activation in osteoclast precursors. In vitro phosphorylation assay demonstrated that harmine directly inhibited DYRK1A-mediated phosphorylation of NFATc1. In vitro phosphorylation assay, harmine treatment of RAW264.7 and bone marrow macrophages, NFATc1 expression analysis Bone Medium 21504804
2012 Cot kinase (Tpl-2) directly phosphorylates all Ca2+/calcineurin-regulated NFAT family members (NFATc1–NFATc4) and increases their protein stability/levels, promoting Ca2+ oscillation/calcineurin-independent osteoclastogenesis. Cot activity was enhanced by osteoblast–osteoclast cell-cell interaction. In vitro kinase assay, co-culture system, Cot overexpression/knockdown in osteoclasts, protein stability analysis Molecular and Cellular Biology High 22615493
2021 SUMOylation of NFATc1 represses IL-2 production in T cells; mice with prevented NFATc1 SUMOylation show elevated IL-2, expanded Tregs, and suppressed autoreactive/alloreactive immune responses. Increased IL-2 from non-SUMOylated NFATc1 counteracts IL-17 and IFN-γ through STAT5 and Blimp-1 induction. Transgenic knock-in mouse (SUMO modification prevented), EAE and graft-versus-host disease models, cytokine profiling, signaling analysis Journal of Experimental Medicine High 32986812
2015 NFATc1 forms a complex with Sox2 to drive EMT reprogramming and maintain pancreatic cancer cells in a stem cell-like state; NFATc1-Sox2-mediated dedifferentiation is opposed by antithetical p53-miR200c signaling. Co-immunoprecipitation of NFATc1-Sox2 complex, genetic mouse models (GEMM), NFATc1 knockdown/overexpression, in vitro EMT assays EMBO Journal High 25586376
2024 The serine synthesis pathway (SSP)-derived α-ketoglutarate is necessary for histone demethylases that remove repressive H3K27me3 marks at the Nfatc1 gene locus, inducing NFATc1 expression and consequent osteoclast maturation. Deletion of the rate-limiting SSP enzyme phosphoglycerate dehydrogenase impairs osteoclast differentiation and increases bone mass. Conditional knockout of PHGDH in osteoclast progenitors, histone methylation ChIP at Nfatc1 locus, pharmacological PHGDH inhibition, α-ketoglutarate metabolite supplementation Nature Metabolism High 38200114
2018 ASXL1 loss induces concordant reduction of inhibitory H3K27me3 and gain of H3K4me3 at the NFATc1 and itgb3 gene loci, leading to increased NFATc1 expression and enhanced osteoclastogenesis. Jmjd3 histone demethylase knockdown in ASXL1-deficient precursors restores H3K27me3 on the NFATc1 promoter and impairs osteoclast formation. Conditional ASXL1 knockout in myeloid cells, ChIP for H3K27me3/H3K4me3 at NFATc1 promoter, Jmjd3 siRNA knockdown Blood Advances High 30266822
2014 NFATc1 regulates the expression of InsP3R2 (type 2 inositol 1,4,5-trisphosphate receptor) by directly binding to the Itpr2 promoter; calcineurin-NFATc signaling drives Itpr2 transcription in cardiomyocytes, creating a positive feedback loop between InsP3R2 and calcineurin-NFATc signaling during cardiac hypertrophy. ChIP for NFATc1 binding at Itpr2 promoter, promoter-reporter assay, cyclosporin A inhibition, calcineurin-A transgenic mice, hypertrophic agonist stimulation Journal of Biological Chemistry High 24415751
2009 VEGF activates NFATc1 via calcineurin and MEK1-ERK1/2-dependent signaling to promote endocardial cushion cell proliferation during valve development; subsequently RANKL inhibits VEGF-induced proliferation while inducing cathepsin K via calcineurin/NFATc1 and JNK1/2-dependent signaling, demonstrating ligand-specific cofactor cooperation. NFATc1-/- mice analysis, chick ECC explant cultures, pharmacological inhibition of calcineurin/MEK/JNK, VEGF/RANKL stimulation Circulation Research High 19661463
2017 The cytoplasmic ITIM motif of DC-STAMP regulates NFATc1 nuclear translocation and expression; deletion of ITIM elevates Ca2+ flux amplitude/duration and alters NFATc1-dependent osteoclast phenotypes. DC-STAMP overexpression restores NFATc1 expression in DC-STAMP-/- cells. Light-activatable DC-STAMP chimeric molecule, Ca2+ flux imaging, ITIM deletion mutants, NFATc1 nuclear translocation assay, DC-STAMP overexpression Journal of Cellular Physiology Medium 27723141
2003 NFATc1 is required cell-intrinsically for normal B-1a cell development; NFATc1 protein is elevated ~5-fold in B-1a cells compared with B-2 cells, and the B-1a compartment is essentially absent in NFATc1-/- mice but normal in NFATc2-/- mice. Mixed-allotype chimeras and retroviral gene transduction confirmed the B cell-intrinsic requirement. NFATc1-/- and NFATc2-/- mouse analysis, mixed-allotype chimeras, retroviral NFATc1 gene transduction, flow cytometry PNAS High 14595020
2017 Gα13 negatively regulates osteoclastogenesis through the RhoA/Akt/GSK3β/NFATc1 signaling pathway; Gna13-deficiency decreases RhoA activity and enhances Akt/GSK3β/NFATc1 signaling. Akt inhibition or RhoA activation rescues the hyper-activation of Gna13-deficient osteoclasts. Osteoclast-lineage-specific Gna13 conditional knockout mice, RNAi, Akt inhibitor and RhoA activator pharmacological rescue, signaling pathway analysis Nature Communications High 28102206
2002 GATA5 and NF-ATc (NFATc1) synergistically activate endocardial transcription; inhibition of either GATA5 expression or NF-ATc activation blocks terminal endocardial differentiation at a pre-endocardial stage, establishing cooperative regulation of endothelial-endocardial differentiation. In vitro cardiogenic differentiation model, inhibition of GATA5 and NF-ATc, reporter assay for endocardial gene expression Development Medium 12163407
2010 Pim-1 kinase interacts with RANK and TAK1 and promotes RANKL-induced NF-κB activation via TAK1; overexpression of dominant-negative Pim-1 blocks RANKL-induced NFATc1 expression and osteoclastogenesis. Pim-1 also regulates NFATc1 transcriptional activity and OSCAR expression. Co-immunoprecipitation (Pim-1 with RANK and TAK1), dominant-negative overexpression, RNA interference, NF-κB and NFATc1 reporter assays Journal of Immunology Medium 21068407
2005 CCR1 (chemokine receptor) acts as a downstream target of NFATc1/NFAT2 in RANKL-stimulated osteoclastogenesis; the CCR1 upstream regulatory region shows RANKL-dependent and cyclosporin A-suppressible promoter activity, and CCR1 silencing suppresses osteoclast precursor migration. Microarray analysis, quantitative RT-PCR, luciferase promoter reporter assay, cyclosporin A inhibition, CCR1 siRNA knockdown, Boyden chamber migration assay Journal of Bone and Mineral Research Medium 16355273
2023 NFATc1 transcriptionally upregulates SLC7A11 expression during RANKL-induced osteoclastogenesis, driving cystine import and sensitivity to TXNRD1 inhibitor-induced disulfidptosis in osteoclast precursors. ChIP for NFATc1 binding at SLC7A11 locus, siRNA knockdown, SLC7A11 inhibitor rescue, in vivo OVX model Redox Biology Medium 37148740
2015 PU.1 directly binds to the NFATc1 promoter in osteoclasts to transactivate NFATc1 expression; PU.1 knockdown reduces NFATc1 mRNA and promoter activity, while enforced PU.1 expression increases NFATc1 and osteoclast differentiation. ChIP for PU.1 binding at NFATc1 promoter, luciferase reporter assay, siRNA knockdown, retroviral enforced expression Allergology International Medium 26117255
2020 Nfatc1 promotes valve interstitial cell (VIC) formation in zebrafish atrioventricular valve by stimulating VIC proliferation and recruitement of endocardial and neural crest cells; nfatc1 mutants form fewer VICs. NFATc1 promotes expression of twist1b, a regulator of epithelial-to-mesenchymal transition, as a downstream effector. Zebrafish nfatc1 mutants, live imaging, high-speed microscopy and echocardiography, downstream effector analysis (twist1b expression) Circulation Research Medium 32070236
2023 The deubiquitinase UCHL1 deubiquitinates and stabilizes TAZ at K46 residue (preventing K48-linked polyubiquitination); stabilized TAZ then competes with calcineurin A for binding to NFATc1, inhibiting NFATc1 dephosphorylation and nuclear transport, thereby negatively regulating osteoclastogenesis. Co-IP (TAZ-NFATc1 and CNA-NFATc1 interaction), ubiquitination assay (K46 site), UCHL1 conditional knockout mice, proteomic analysis, OVX bone loss model International Journal of Biological Sciences Medium 37215988
2019 Homer2 and Homer3 scaffold proteins regulate NFATc1 function by interacting with NFATc1 and modulating its interaction with calcineurin; RANKL treatment inhibits Homer protein interaction with NFATc1 (restored by cyclosporin A treatment). Homer2/3 double knockout increases NFATc1 expression and nuclear translocation without altering Ca2+ oscillations, demonstrating a Ca2+-independent regulation of NFATc1-calcineurin interaction. Homer2/3 double knockout mice, Co-IP of Homer proteins with NFATc1 and calcineurin, cyclosporin A treatment, Ca2+ oscillation measurement, NFATc1 nuclear translocation assay Journal of Endocrinology Medium 31319381
2016 The transcriptional coactivator/repressor Ifrd1 enhances NF-κB/NFATc1 signaling in osteoclasts; Ifrd1 deficiency increases p65 acetylation at K122/K123 via impaired histone deacetylase-dependent deacetylation, repressing NF-κB-dependent NFATc1 transcription and reducing osteoclastogenesis. Ifrd1 global and conditional knockout mice, histone acetylation analysis of p65, HDAC inhibitor studies, NFATc1 reporter and expression analysis Molecular and Cellular Biology Medium 27381458
2019 RBP-J represses miR182 expression while NFATc1 activates miR182 transcription through binding to specific open chromatin regions in the miR182 promoter; RBP-J inhibition of miR182 limits TNF-induced osteoclast differentiation and inflammatory bone resorption. ChIP for NFATc1 and RBP-J binding at miR182 promoter, ATAC-seq for open chromatin, in vivo inflammatory arthritis model, TNF inhibitor treatment of RA patients FASEB Journal Medium 31908034
2011 NFATc1 regulates TRAIL expression in intestinal cells through negative regulation of Sp1 binding to the TRAIL promoter; NFATc1 activation increases TRAIL expression by repressing Sp1 transcription factor binding to the TRAIL promoter. NFATc1 siRNA knockdown, NFATc1 overexpression, TRAIL promoter reporter assay with NFAT site deletion, ChIP for Sp1 binding, Sp1 chemical inhibition and siRNA PLoS ONE Medium 21603612
2014 NFATc1 activity regulates dexamethasone-induced myocilin (MYOC) expression in human trabecular meshwork cells; dexamethasone induces calcineurin-dependent NFATc1 nuclear translocation within 15 minutes in a calcium-independent mechanism, and NFATc1 siRNA knockdown reduces MYOC mRNA induction. NFATc1 siRNA knockdown, calcineurin inhibitors (cyclosporin A, INCA-6), immunofluorescence for NFATc1 nuclear translocation, ionomycin treatment control Experimental Eye Research Medium 25450062
2009 FOXP3 competes with NFAT1 for binding to the endogenous NFAT2 (NFATc1) promoter, suppressing NFATc1 transcription in regulatory T cells; ectopic NFAT2 expression partially restores IL-2 production in FOXP3+ Tregs, demonstrating that FOXP3-mediated repression of NFATc1 contributes to T cell anergy. ChIP for FOXP3 and NFAT1 at NFATc1 promoter, inducible FOXP3-expressing cell lines, retroviral NFAT2 overexpression, IL-2 reporter assay Journal of Immunology Medium 19564342
2022 Cav2.2 (voltage-gated calcium channel) upregulates USP43 deubiquitinase expression through NFAT2 (NFATc1) dephosphorylation and nuclear localization, which then stabilizes cortactin to promote invadopodia formation and breast cancer metastasis. Co-immunoprecipitation, siRNA knockdown of Cav2.2/NFAT2/USP43, NFATc1 nuclear localization imaging, invasion assay, in vivo metastasis model Cell Death & Disease Medium 36137995
2022 NFATc1 drives NAFLD progression through ER stress sensing and activation of the PERK-CHOP unfolded protein response (UPR) in hepatocytes; hepatocyte-specific NFATc1 depletion prevents disease acceleration in high-fat western diet-fed mice, and NFATc1 activation induces NLRP3 inflammasome activation. Hepatocyte-specific NFATc1 conditional knockout and overexpression transgenic mice, high-fat diet model, PERK-CHOP pathway analysis, NLRP3 inflammasome activation assay, TUDCA pharmacological inhibition Gut High 35365570
2019 CR3 engagement by M. leprae PGL-I activates the Syk tyrosine kinase, inducing calcineurin-dependent nuclear translocation of NFATc in innate immune cells (macrophages, neutrophils, dendritic cells), selectively augmenting production of IL-2 (DCs), IL-10 (PMNs), and IL-1β (macrophages). CR3 engagement assay, Syk kinase inhibitor, calcineurin inhibitor, NFATc nuclear translocation imaging, cytokine measurement in infected mice Frontiers in Immunology Medium 31921172

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Developmental cell 2078 12479813
2005 Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. The Journal of experimental medicine 714 16275763
1997 Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science (New York, N.Y.) 624 9072970
1998 The transcription factor NF-ATc is essential for cardiac valve formation. Nature 476 9515964
2014 Regulation of NFATc1 in Osteoclast Differentiation. Journal of bone metabolism 437 25489571
2008 NFATc1 balances quiescence and proliferation of skin stem cells. Cell 348 18243104
2008 NFATc1 regulates PD-1 expression upon T cell activation. Journal of immunology (Baltimore, Md. : 1950) 330 18802087
2019 Loureirin B suppresses RANKL-induced osteoclastogenesis and ovariectomized osteoporosis via attenuating NFATc1 and ROS activities. Theranostics 174 31367247
2002 Autoregulation of NFATc1/A expression facilitates effector T cells to escape from rapid apoptosis. Immunity 166 12121669
1995 NFATc3, a lymphoid-specific NFATc family member that is calcium-regulated and exhibits distinct DNA binding specificity. The Journal of biological chemistry 161 7650004
2001 Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers. The Journal of cell biology 145 11581284
2007 MITF and PU.1 recruit p38 MAPK and NFATc1 to target genes during osteoclast differentiation. The Journal of biological chemistry 142 17403683
2000 Glycogen synthase kinase-3 inhibits the DNA binding activity of NFATc. The Journal of biological chemistry 129 11063740
2000 Identification of amino acid residues and protein kinases involved in the regulation of NFATc subcellular localization. The Journal of biological chemistry 122 10652349
2017 Gα13 negatively controls osteoclastogenesis through inhibition of the Akt-GSK3β-NFATc1 signalling pathway. Nature communications 119 28102206
2019 Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca2+-NFATc1 signaling pathway. Acta pharmacologica Sinica 105 31431733
2002 NFAT1 and NFAT2 are positive regulators of IL-4 gene transcription. European journal of immunology 105 12355451
2014 Inflammation-induced NFATc1-STAT3 transcription complex promotes pancreatic cancer initiation by KrasG12D. Cancer discovery 104 24694735
1998 Solution structure of the core NFATC1/DNA complex. Cell 97 9506523
2019 STAT3 controls osteoclast differentiation and bone homeostasis by regulating NFATc1 transcription. The Journal of biological chemistry 92 31462535
2015 Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity. The EMBO journal 85 25586376
2012 Strontium ranelate rebalances bone marrow adipogenesis and osteoblastogenesis in senescent osteopenic mice through NFATc/Maf and Wnt signaling. Aging cell 82 22321691
2020 The Role of Ca2+-NFATc1 Signaling and Its Modulation on Osteoclastogenesis. International journal of molecular sciences 80 32455661
2023 NFATc1-mediated expression of SLC7A11 drives sensitivity to TXNRD1 inhibitors in osteoclast precursors. Redox biology 79 37148740
2002 Cooperative interaction between GATA5 and NF-ATc regulates endothelial-endocardial differentiation of cardiogenic cells. Development (Cambridge, England) 78 12163407
2013 NFAT2 inhibitor ameliorates diabetic nephropathy and podocyte injury in db/db mice. British journal of pharmacology 73 23826864
2006 NFATc1 autoregulation: a crucial step for cell-fate determination. Trends in immunology 62 16931157
2021 Dendrobine attenuates osteoclast differentiation through modulating ROS/NFATc1/ MMP9 pathway and prevents inflammatory bone destruction. Phytomedicine : international journal of phytotherapy and phytopharmacology 57 34801352
2003 Normal B-1a cell development requires B cell-intrinsic NFATc1 activity. Proceedings of the National Academy of Sciences of the United States of America 57 14595020
2019 AP-1 and Mitf interact with NFATc1 to stimulate cathepsin K promoter activity in osteoclast precursors. Journal of cellular biochemistry 56 30816596
2009 VEGF and RANKL regulation of NFATc1 in heart valve development. Circulation research 56 19661463
2022 NFATc1 signaling drives chronic ER stress responses to promote NAFLD progression. Gut 54 35365570
2018 Knockdown of TRPV4 suppresses osteoclast differentiation and osteoporosis by inhibiting autophagy through Ca2+ -calcineurin-NFATc1 pathway. Journal of cellular physiology 53 30387123
2013 AG490 inhibits NFATc1 expression and STAT3 activation during RANKL induced osteoclastogenesis. Biochemical and biophysical research communications 50 23665018
2006 Regulation of Th2 cytokine expression in NKT cells: unconventional use of Stat6, GATA-3, and NFAT2. Journal of immunology (Baltimore, Md. : 1950) 50 16393972
2016 Accelerated Lactate Dehydrogenase Activity Potentiates Osteoclastogenesis via NFATc1 Signaling. PloS one 49 27077737
2012 Calcineurin/NFATc1 pathway contributes to cell proliferation in hepatocellular carcinoma. Digestive diseases and sciences 48 22722879
2020 Nfatc1 Promotes Interstitial Cell Formation During Cardiac Valve Development in Zebrafish. Circulation research 47 32070236
2011 NFATC1 promotes epicardium-derived cell invasion into myocardium. Development (Cambridge, England) 47 21447555
2012 Ginsenoside Rh2 inhibits osteoclastogenesis through down-regulation of NF-κB, NFATc1 and c-Fos. Bone 46 22484180
2020 Arctiin abrogates osteoclastogenesis and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation. Pharmacological research 44 32454224
2013 NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression. Experimental cell research 43 23340267
2011 The small molecule harmine regulates NFATc1 and Id2 expression in osteoclast progenitor cells. Bone 38 21504804
2024 The serine synthesis pathway drives osteoclast differentiation through epigenetic regulation of NFATc1 expression. Nature metabolism 37 38200114
2019 Berberine Suppresses RANKL-Induced Osteoclast Differentiation by Inhibiting c-Fos and NFATc1 Expression. The American journal of Chinese medicine 37 30827151
2015 NFATc1 promotes prostate tumorigenesis and overcomes PTEN loss-induced senescence. Oncogene 37 26477312
2014 Calcineurin-NFATc regulates type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2) expression during cardiac remodeling. The Journal of biological chemistry 37 24415751
2010 Pim-1 regulates RANKL-induced osteoclastogenesis via NF-κB activation and NFATc1 induction. Journal of immunology (Baltimore, Md. : 1950) 37 21068407
2019 TRPV1 Induced Apoptosis of Colorectal Cancer Cells by Activating Calcineurin-NFAT2-p53 Signaling Pathway. BioMed research international 36 31183372
2013 NFATc1 induction in peripheral T and B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 36 23365084
2017 AKAP150 involved in paclitaxel-induced neuropathic pain via inhibiting CN/NFAT2 pathway and downregulating IL-4. Brain, behavior, and immunity 35 29056557
2009 FOXP3 inhibits activation-induced NFAT2 expression in T cells thereby limiting effector cytokine expression. Journal of immunology (Baltimore, Md. : 1950) 35 19564342
2022 Ginsenoside Rg1 attenuates glomerular fibrosis by inhibiting CD36/TRPC6/NFAT2 signaling in type 2 diabetes mellitus mice. Journal of ethnopharmacology 34 36375645
2018 TRPM3/TRPV4 regulates Ca2+-mediated RANKL/NFATc1 expression in osteoblasts. Journal of molecular endocrinology 34 30328352
2007 Reciprocal NFAT1 and NFAT2 nuclear localization in CD8+ anergic T cells is regulated by suboptimal calcium signaling. Journal of immunology (Baltimore, Md. : 1950) 34 17785810
2018 MicroRNA-499-5p regulates skeletal myofiber specification via NFATc1/MEF2C pathway and Thrap1/MEF2C axis. Life sciences 33 30419283
2017 Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) Regulates Osteoclast Differentiation via the Ca2+ /NFATc1 Axis. Journal of cellular physiology 33 27723141
2019 Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis via NF-κB-NFATc1 signal pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 30857415
2005 CCR1 acts downstream of NFAT2 in osteoclastogenesis and enhances cell migration. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32 16355273
2021 Major vault protein (MVP) negatively regulates osteoclastogenesis via calcineurin-NFATc1 pathway inhibition. Theranostics 30 34158848
2017 NFATC1 activation by DNA hypomethylation in chronic lymphocytic leukemia correlates with clinical staging and can be inhibited by ibrutinib. International journal of cancer 29 28921505
2015 NFAT1 deficit and NFAT2 deficit attenuate EAE via different mechanisms. European journal of immunology 29 25630465
2014 Mitf regulates osteoclastogenesis by modulating NFATc1 activity. Experimental cell research 29 25152440
2020 TGFβ1 Regulates Human RANKL-Induced Osteoclastogenesis via Suppression of NFATc1 Expression. International journal of molecular sciences 28 31991837
2017 Ca2+-Dependent Regulation of NFATc1 via KCa3.1 in Inflammatory Osteoclastogenesis. Journal of immunology (Baltimore, Md. : 1950) 27 29246953
2014 Arginine enhances osteoblastogenesis and inhibits adipogenesis through the regulation of Wnt and NFATc signaling in human mesenchymal stem cells. International journal of molecular sciences 27 25054323
2021 Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity. The Journal of experimental medicine 26 32986812
2018 ASXL1 impairs osteoclast formation by epigenetic regulation of NFATc1. Blood advances 26 30266822
2016 Transcriptional Modulator Ifrd1 Regulates Osteoclast Differentiation through Enhancing the NF-κB/NFATc1 Pathway. Molecular and cellular biology 26 27381458
2023 RhoA promotes osteoclastogenesis and regulates bone remodeling through mTOR-NFATc1 signaling. Molecular medicine (Cambridge, Mass.) 25 37020186
2017 NFATc1 phosphorylation by DYRK1A increases its protein stability. PloS one 25 28235034
2004 Sculpting heart valves with NFATc and VEGF. Cell 25 15339657
2020 Renal tubular Bim mediates the tubule-podocyte crosstalk via NFAT2 to induce podocyte cytoskeletal dysfunction. Theranostics 24 32550905
2017 TNFα Increases RANKL Expression via PGE₂-Induced Activation of NFATc1. International journal of molecular sciences 24 28245593
2022 Cav2.2-NFAT2-USP43 axis promotes invadopodia formation and breast cancer metastasis through cortactin stabilization. Cell death & disease 23 36137995
2017 Gastrodin inhibits osteoclastogenesis via down-regulating the NFATc1 signaling pathway and stimulates osseointegration in vitro. Biochemical and biophysical research communications 23 28161640
2015 Involvement of PU.1 in NFATc1 promoter function in osteoclast development. Allergology international : official journal of the Japanese Society of Allergology 23 26117255
2014 NFATc1 activity regulates the expression of myocilin induced by dexamethasone. Experimental eye research 23 25450062
2020 Role of NFATc1 in the Bone-Vascular Axis Calcification Paradox. Journal of cardiovascular pharmacology 22 31868826
2019 MiR-30 family prevents uPAR-ITGB3 signaling activation through calcineurin-NFATC pathway to protect podocytes. Cell death & disease 22 31127093
2018 Fluid shear stress promotes osteoblast proliferation through the NFATc1-ERK5 pathway. Connective tissue research 22 29609502
2015 Identification of small-molecule inhibitors of calcineurin-NFATc signaling that mimic the PxIxIT motif of calcineurin binding partners. Science signaling 22 26106221
2021 HIF-Dependent NFATC1 Activation Upregulates ITGA5 and PLAUR in Intestinal Epithelium in Inflammatory Bowel Disease. Frontiers in genetics 21 34858489
2020 miR-506-3p alleviates uncontrolled osteoclastogenesis via repression of RANKL/NFATc1 signaling pathway. Journal of cellular physiology 21 32372426
2019 NFAT1 and NFAT2 Differentially Regulate CTL Differentiation Upon Acute Viral Infection. Frontiers in immunology 21 30828328
2012 Lithium regulates keratinocyte proliferation via glycogen synthase kinase 3 and NFAT2 (nuclear factor of activated T cells 2). Journal of cellular physiology 21 21678407
2022 Osteostatin Inhibits M-CSF+RANKL-Induced Human Osteoclast Differentiation by Modulating NFATc1. International journal of molecular sciences 19 35955685
2012 Cot kinase promotes Ca2+ oscillation/calcineurin-independent osteoclastogenesis by stabilizing NFATc1 protein. Molecular and cellular biology 19 22615493
2020 Dehydrocostus lactone inhibits NFATc1 via regulation of IKK, JNK, and Nrf2, thereby attenuating osteoclastogenesis. BMB reports 18 31964469
2019 Regulatory network mediated by RBP-J/NFATc1-miR182 controls inflammatory bone resorption. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 31908034
2019 CR3 Engaged by PGL-I Triggers Syk-Calcineurin-NFATc to Rewire the Innate Immune Response in Leprosy. Frontiers in immunology 18 31921172
2011 NFATc1 regulation of TRAIL expression in human intestinal cells. PloS one 18 21603612
2023 The deubiquitinase UCHL1 negatively controls osteoclastogenesis by regulating TAZ/NFATC1 signalling. International journal of biological sciences 17 37215988
2019 Homer2 and Homer3 modulate RANKL-induced NFATc1 signaling in osteoclastogenesis and bone metabolism. The Journal of endocrinology 17 31319381
2018 B cell development is critically dependent on NFATc1 activity. Cellular & molecular immunology 17 29907883
2011 Retinoic acid inhibits NFATc1 expression and osteoclast differentiation. Journal of bone and mineral metabolism 17 21384111
2024 FPR3 reprograms glycolytic metabolism and stemness in gastric cancer via calcium-NFATc1 pathway. Cancer letters 16 38614385
2019 High expression of NFAT2 contributes to carboplatin resistance in lung cancer. Experimental and molecular pathology 16 31362013
2014 NF-κB factors control the induction of NFATc1 in B lymphocytes. European journal of immunology 16 25179582
2000 Grb3-3 is up-regulated in HIV-1-infected T-cells and can potentiate cell activation through NFATc. The Journal of biological chemistry 16 10906142