Affinage

NFATC2

Nuclear factor of activated T-cells, cytoplasmic 2 · UniProt Q13469

Length
925 aa
Mass
100.1 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFATC2 (NFATp/NFAT1) is a calcium/calcineurin-regulated transcription factor that converts T-cell receptor and other Ca2+-mobilizing signals into programs of cytokine gene expression and broader cell-fate decisions (PMID:8235597, PMID:7545680). In resting cells it is a hyperphosphorylated, DNA-binding-incompetent phosphoprotein; calcineurin binds NFATC2 directly through a conserved N-terminal region and dephosphorylates it, restoring DNA binding and driving nuclear accumulation, while cessation of Ca2+ signaling, cyclosporin A, or FK506-FKBP12 reverses these steps and re-exports the protein (PMID:8397339, PMID:7657645, PMID:8576111, PMID:8631904). The activation cycle is closed by kinases that rephosphorylate NFATC2 to promote CRM1-dependent nuclear export and turnover: p38 MAPK opposes its nuclear accumulation (PMID:10788511), and GSK-3β both targets NFAT for proteasomal degradation downstream of Akt (PMID:19258413) and, paradoxically in pancreatic cancer, stabilizes nuclear NFATC2 and its STAT3 complexes to maintain target-gene chromatin in an active state (PMID:26823495). Once nuclear, NFATC2 acts as the DNA-binding subunit of composite enhancer complexes, cooperating with AP-1 (Fos-Jun) and ATF-2/Jun on spacing-constrained NFAT-AP-1 elements of IL-2, GM-CSF, and TNF-α promoters, where it locks AP-1 orientation and bends DNA through specific protein-protein contacts (PMID:8397339, PMID:8552071, PMID:7891702, PMID:7583146, PMID:9653115). Structurally it binds DNA as a monomer or as a novel asymmetric Rel-homology dimer, and the dimer form carries activation subdomains that recruit the CBP coactivator (PMID:12949493, PMID:19060202). Through these complexes NFATC2 drives cytokine and effector genes (TNF-α, IL-4, IL-21) and mediates T-cell anergy and B-cell tolerance (PMID:7982959, PMID:12093869, PMID:15684054, PMID:16849457, PMID:22865456), and it also functions as a sequence-specific repressor, silencing CDK4 and the p15(INK4b) locus via Suv39H1/H3K9me3/HP1γ heterochromatin assembly and repressing CX3CR1 (PMID:12453415, PMID:22079596, PMID:15347678). Beyond immunity, NFATC2 is intrinsically required for skeletal myotube growth and nuclear accretion downstream of prostaglandin F2α/FP signaling (PMID:11309414, PMID:12695501), represses chondrogenesis (PMID:10620601), and drives β-cell proliferation through Nr4a1 and FOXP cofactors (PMID:34491912). In cancer it is aberrantly activated to transcribe MDM2, MMP3, MMP-9, IL8, the SOX2/ALDH1A1 stemness-and-drug-resistance axis, and Ets1, promoting invasion, metastasis, and tumor-initiating-cell self-renewal (PMID:22787160, PMID:27013197, PMID:28737489, PMID:32339381, PMID:30467308).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1993 High

    Established the foundational identity of NFATC2 as the DNA-binding subunit of the NFAT complex and as a direct calcineurin substrate that builds ternary complexes with AP-1.

    Evidence Protein purification, cDNA cloning, recombinant DNA-binding and reporter assays, and in vitro calcineurin phosphatase assays with Fos/Jun DNA-binding-domain mutagenesis

    PMID:8235597 PMID:8397339

    Open questions at the time
    • Did not define the in vivo phosphorylation sites controlling activity
    • Cellular kinetics of translocation not yet resolved
  2. 1995 High

    Resolved the regulatory logic: phosphorylation directly blocks DNA binding and calcineurin-mediated dephosphorylation upon Ca2+ signaling triggers nuclear translocation, defining the on-switch.

    Evidence 32P labeling, in vitro calcineurin/alkaline phosphatase treatment, EMSA, and subcellular fractionation with FK506 inhibition in T cells

    PMID:7545680 PMID:7657645

    Open questions at the time
    • Calcineurin docking interface on NFATC2 not yet mapped
    • Off-switch kinases not identified
  3. 1996 High

    Mapped the physical calcineurin–NFATC2 interaction and showed calcineurin activity bidirectionally controls activation state, completing the reversible activation/deactivation cycle.

    Evidence Calcineurin pulldown with FK506-FKBP12 competition; pharmacological manipulation (EGTA, CsA, ionomycin, PMA) with fractionation and EMSA

    PMID:8576111 PMID:8631904 PMID:8668212

    Open questions at the time
    • Identity of the rephosphorylating kinases for export not yet established
    • Capacitative Ca2+ entry link only pharmacologically inferred
  4. 1995 High

    Defined the biochemical basis of cooperative NFAT-AP-1 enhancer assembly, showing strict spacing requirements and NFATC2-imposed AP-1 orientation that distinguish functional from non-functional composite sites.

    Evidence EMSA, methylation interference, DNase footprinting, affinity-cleaving, cross-linking and reporter assays on GM-CSF and IL-2 elements

    PMID:7583146 PMID:7891702

    Open questions at the time
    • Structural basis of the orientation lock not yet visualized
    • Coactivator recruitment not yet addressed
  5. 1994 High

    Extended NFATC2 target repertoire to the TNF-α promoter, showing dual-site occupancy and cooperation with adjacent ATF-2/Jun is required for calcium-driven, CsA-sensitive induction.

    Evidence EMSA, promoter-reporter assays, site mutagenesis, and CsA inhibition in T cells

    PMID:7982959 PMID:8552071

    Open questions at the time
    • Whether monomer vs dimer binding distinguishes TNF-α regulation not yet resolved
  6. 1999 High

    Identified VDR as a competitive repressor that blocks NFATC2/AP-1 complex formation at IL-2 and GM-CSF elements, revealing transcription-factor competition as a mode of NFAT regulation.

    Evidence In vitro competition with purified proteins, EMSA, GST coprecipitation with c-Jun, FLAG-VDR IP, and reporter rescue by NFAT overexpression

    PMID:10330159 PMID:7565732

    Open questions at the time
    • Physiological contexts where VDR competition dominates not defined
  7. 2003 High

    Provided the structural mechanism by solving the NFATC2 dimer on a κB element, revealing a novel asymmetric Rel-homology dimerization mode distinct from other Rel proteins.

    Evidence X-ray crystallography of NFAT1 bound to HIV-1 LTR κB DNA; FRET/phasing analysis of cooperative DNA bending in the ternary complex

    PMID:12949493 PMID:9653115

    Open questions at the time
    • Functional consequence of dimerization not yet established at the time
  8. 2008 High

    Linked the dimer structure to function, showing NFATC2 dimer-specific activation subdomains recruit CBP and confer dimer-dependent transcriptional output at the TNF element.

    Evidence Consensus site determination, DNase footprinting, transcriptional reporters, and coactivator interaction assays

    PMID:19060202

    Open questions at the time
    • In vivo prevalence of dimer vs monomer binding genome-wide unknown
  9. 2000 High

    Identified kinase off-switches: p38 MAPK phosphorylates and drives CRM1-dependent export of NFATC2, distinguishing its regulation from NFATc.

    Evidence In vitro kinase assay, co-IP, activated MKK6/p38 cotransfection, fractionation, and Leptomycin B inhibition

    PMID:10788511

    Open questions at the time
    • Phospho-acceptor sites for p38 on NFATC2 not mapped
  10. 2001 High

    Demonstrated a non-immune, cell-intrinsic role: NFATC2 is required for a second phase of myoblast fusion and skeletal myotube growth.

    Evidence NFATC2-null primary myotubes, retroviral rescue, and morphometric measurement of size and myonuclear number

    PMID:11309414

    Open questions at the time
    • Direct muscle-growth target genes not identified
  11. 2003 High

    Placed prostaglandin F2α/FP receptor signaling upstream of NFATC2 in muscle growth, the first prostaglandin-receptor–NFAT intersection.

    Evidence PGF2α treatment, NFAT reporter, and NFATC2-null myotube nuclear accretion assays

    PMID:12695501

    Open questions at the time
    • Signaling steps linking FP receptor to calcineurin in muscle not detailed
  12. 2000 High

    Revealed NFATC2 as a repressor of differentiation: loss causes spontaneous cartilage formation, establishing it as a brake on chondrogenesis.

    Evidence NFATp knockout mouse histology and chondrocyte-line overexpression with cartilage-marker analysis

    PMID:10620601

    Open questions at the time
    • Repressed chondrogenic target genes not molecularly defined
  13. 2004 High

    Showed cytokine-context selectivity in repression: IL-15 recruits NFATC2 specifically to repress CX3CR1, contrasting with IL-2/NFAT2 activation of the same gene.

    Evidence ChIP for NFAT1/NFAT2, NFAT1 KO mice, CsA/VIVIT inhibitors, and κB-NFAT site mutation reporter assays

    PMID:15347678

    Open questions at the time
    • Mechanism converting NFATC2 from activator to repressor at this site unresolved
  14. 2002 High

    Defined direct gene-control roles in immune differentiation and cell cycle: NFATC2 drives IL-4 (downstream of IL-6) and IL-21, and represses CDK4 via HDAC-sensitive promoter binding.

    Evidence NFATc2 KO T cells, IL-4 ELISA, NFAT reporters, ChIP/EMSA at IL-21, CDK4 promoter-reporters and CDK4 levels in calcineurin/NFATc2 KO mice

    PMID:12093869 PMID:12355451 PMID:12453415 PMID:15684054

    Open questions at the time
    • Switch between activator and repressor functions at different promoters not mechanistically unified
  15. 2006 Medium

    Established NFATC2 as an enforcer of tolerance/anergy in both B and T lymphocytes, framing it as a negative as well as positive immune regulator.

    Evidence NFAT1 KO crossed with anti-lysozyme anergy model; NFAT1-deficient antigen-specific CD4+ T cells in melanoma model

    PMID:16849457 PMID:22865456

    Open questions at the time
    • Anergy-associated gene targets only partially defined
    • Single-lab models for each phenotype
  16. 2012 High

    Identified oncogenic activation routes: VRK2 phosphorylates NFAT1 at Ser-32 to boost COX-2-driven invasion, and NFAT1 transactivates MDM2 to suppress p53.

    Evidence In vitro kinase assay (Ser-32), co-IP, EMSA/ChIP at mdm2 P2 promoter, reporters, and invasion assays

    PMID:22787160 PMID:23105117

    Open questions at the time
    • Whether VRK2 and the calcineurin axis converge on the same activation pool unknown
  17. 2016 High

    Resolved a context-specific GSK-3β role and chromatin mechanism in pancreatic cancer: GSK-3β stabilizes nuclear NFATc2 and NFATc2-STAT3 complexes, while NFATc2 builds Suv39H1/H3K9me3/HP1γ heterochromatin to silence p15(INK4b).

    Evidence Co-IP, ChIP (H3K9me3, target promoters), DNA pulldown, reporters, and xenograft/GEMM models

    PMID:22079596 PMID:26823495

    Open questions at the time
    • Reconciliation with GSK-3β-driven NFAT degradation in other contexts not fully resolved
  18. 2009 Medium

    Placed NFAT downstream of Akt-GSK-3β signaling controlling proteasomal turnover and breast cancer migration, defining a degradation-based off-switch.

    Evidence GSK-3β shRNA/inhibitor, Akt-unresponsive GSK-3β mutants, NFAT reporter, proteasome inhibitors, and migration assays

    PMID:19258413

    Open questions at the time
    • Degradation machinery and ubiquitin ligase not identified
    • Single lab
  19. 2017 Medium

    Defined NFATC2 cancer transcriptional programs driving invasion, metastasis, stemness, and drug resistance through direct targets including IL8, MMP3, MMP-9, Ets1, and the SOX2/ALDH1A1 axis.

    Evidence ChIP/reporters at target promoters and enhancers, knockdown/rescue, Ca2+/calcineurin assays, CRISPR CRE deletion, sphere and xenograft/metastasis assays

    PMID:25735562 PMID:26387540 PMID:27013197 PMID:28737489 PMID:30467308 PMID:32339381 PMID:33754043

    Open questions at the time
    • Many targets validated in single tumor types and single labs
    • Direct ChIP missing for some targets
  20. 2021 High

    Mapped genome-wide NFATC2 programs in non-immune proliferation and epigenetic activation: ~2200 β-cell targets via Nr4a1 and FOXP cofactors, and dectin-1–induced H3K4me3 deposition at cytokine loci in dendritic cells.

    Evidence Active NFATC2 expression in human islets with RNA-seq/ChIP-seq/ATAC-seq, FOXP and Nr4a1 KO; ChIP-seq and H3K4me3 ChIP in dendritic cells

    PMID:25550437 PMID:34491912

    Open questions at the time
    • Direct biochemical link between NFATC2 and the H3K4 methyltransferase not established
  21. 2022 High

    Extended NFATC2 regulation to T-cell exhaustion and microglial neuroinflammation: Dapl1/Tim3 restrains NFATc2 in CD8+ T cells, and LRRK2 phosphorylates NFATc2 to drive cytokine production via direct binding of inflammatory and proliferative promoters.

    Evidence Dapl1 KO mice with adoptive transfer/tumor models; LRRK2 KO/inhibition with nuclear fractionation and ELISA; microglia-specific Nfat1 KO with ChIP at Itgam/Tnf/Il1b/c-Myc

    PMID:33055242 PMID:35773432 PMID:35892263

    Open questions at the time
    • LRRK2 phospho-site on NFATc2 not mapped
    • Interplay between calcineurin and these alternative kinase inputs unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NFATC2 is switched between activator and repressor at a given locus, and how competing kinase inputs (calcineurin, p38, GSK-3β, VRK2, LRRK2) are integrated to set monomer vs dimer occupancy genome-wide, remains unresolved.
  • No unified model linking phosphorylation state to activator/repressor choice
  • Determinants of monomer vs dimer binding in vivo unknown
  • Cofactor code (CBP vs Suv39H1/HP1γ) selection not mechanistically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 6 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0005634 nucleus 6 GO:0005654 nucleoplasm 3 GO:0005829 cytosol 3
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 6 R-HSA-168256 Immune System 6 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2
Partners
ATF2CREBBP (CBP)FOSJUNPPP3 (CALCINEURIN)STAT3STAT5VDR
Complex memberships
NFAT-AP-1 (Fos-Jun) ternary complexNFATC2 asymmetric homodimerNFATc2-STAT3 complexNFATc2-Suv39H1-HP1γ repressor complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 NFATp (NFATC2) is a DNA-binding phosphoprotein that is a direct substrate for the phosphatase calcineurin in vitro, and forms a ternary complex with Fos and Jun proteins on composite DNA elements; the DNA-binding domains of Fos and Jun are required for NFATp-Fos-Jun-DNA complex formation. In vitro calcineurin phosphatase assay with purified NFATp; recombinant protein DNA-binding assays with Fos/Jun; mutagenesis of Fos/Jun DNA-binding domains Nature High 8397339
1993 NFATp is the DNA-binding subunit of the NFAT transcription complex; a recombinant truncated form binds specifically to the NFAT site of the murine IL-2 promoter and forms a transcriptionally active complex. Protein purification from murine T cells; cDNA cloning; recombinant protein DNA-binding assay; reporter transcription assay Science High 8235597
1995 Phosphorylation of NFATp inhibits its DNA-binding activity and its ability to form an NFAT complex with Fos and Jun; dephosphorylation by calcineurin or alkaline phosphatase in vitro restores DNA binding and complex formation with Fos/Jun. Immunoblot, 32P metabolic labeling, in vitro calcineurin/alkaline phosphatase treatment, EMSA The Journal of biological chemistry High 7657645
1995 NFATp undergoes calcineurin-dependent dephosphorylation and nuclear translocation upon ionomycin stimulation in T cells; immunoprecipitated NFATp from unstimulated cells is dephosphorylated by calcineurin in vitro, confirming it is an in vitro calcineurin substrate. Subcellular fractionation, Western blot, immunoprecipitation, 32P labeling, in vitro calcineurin dephosphorylation assay, FK506 inhibition The Journal of biological chemistry High 7545680
1996 NFAT1 (NFATp/NFATC2) directly interacts with calcineurin through an N-terminal region conserved among NFAT family members; both phosphorylated and dephosphorylated forms of NFATp bind calcineurin, and this binding is blocked by the FK506-FKBP12 complex. Pulldown of NFATp from T cell lysates on immobilized calcineurin; inhibition with FK506-FKBP12 complex The Journal of biological chemistry High 8576111 8631904
1996 Calcineurin activity levels directly control the activation state of NFAT1: cessation of calcium signaling (EGTA, ionomycin removal) or addition of cyclosporin A causes rapid rephosphorylation of NFAT1 and its re-export to the cytoplasm, reversing nuclear accumulation and DNA binding. Subcellular fractionation, Western blot, cyclosporin A/EGTA/ionomycin pharmacological manipulation in T cells The Journal of biological chemistry High 8631904
1994 NFATp binds to two sites within the κ3 element of the TNF-α promoter, and occupancy of both sites is required for calcium-stimulated, cyclosporin A-sensitive TNF-α gene induction in T cells. EMSA, promoter-reporter assays, cyclosporin A inhibition, site mutagenesis The Journal of biological chemistry High 7982959
1996 NFATp cooperates with ATF-2/Jun bound to an adjacent CRE site for TNF-α gene transcription in T cells; ATF-2 and Jun bind noncooperatively with NFATp in vitro, but the composite CRE/κ3 site shows dramatically higher transcriptional activity than κ3 alone, indicating in vivo cooperation. EMSA, promoter-reporter assays, T cell stimulation Molecular and cellular biology High 8552071
1995 On the GM-CSF enhancer composite elements, NFATp and AP-1 bind cooperatively, and this cooperativity requires a specific spacing (9 bp) between GGA and TCA motifs; a site with 15 bp spacing supports strong independent but no cooperative binding of AP-1 and NFATp and functions poorly as an enhancer. EMSA, methylation interference, DNase footprinting, reporter assays Molecular and cellular biology High 7891702
1995 In the cooperative NFAT-AP-1 complex on the IL-2 ARRE2 element, AP-1 (Fos-Jun) adopts a single orientation (Jun proximal, Fos distal to NFATp) through protein-protein contacts; in solution AP-1 binds as a mixture of orientational isomers, but NFATp locks a single orientation. Affinity cleaving experiments, protein cross-linking, EMSA Current biology High 7583146
1995 The vitamin D receptor (VDR) directly competes with NFATp/AP-1 complex formation at the NF-AT-1 element of the IL-2 promoter; VDR-RXR heterodimer blocks NFATp/AP-1 complex formation and stably associates with the NF-AT-1 element; VDR DNA-binding is necessary but not sufficient for repression. In vitro competition assays with partially purified proteins, order-of-addition and off-rate experiments, cotransfection reporter assays, VDR DNA-binding domain mutants Molecular and cellular biology High 7565732
1999 VDR competes with NFAT1 for binding to the GM-CSF NFAT-AP-1 composite site; overexpression of NFAT1 relieves VDR-dependent repression; VDR also directly interacts with c-Jun (demonstrated by GST coprecipitation) and stabilizes Jun-Fos binding adjacent to the NFAT1 binding site, providing a two-hit inhibitory mechanism. Transient transfection reporter assays, EMSA competition, GST coprecipitation, FLAG-VDR immunoprecipitation from nuclear extracts Molecular and cellular biology High 10330159
1996 TCR stimulation leads to rapid (<minutes) calcineurin-dependent dephosphorylation, nuclear translocation, and increased DNA binding of NFAT1, followed hours later by phorbol ester-facilitated rephosphorylation and cytoplasmic re-export; late deactivation is facilitated by PKC-dependent pathways and inhibitors of capacitative calcium entry. Subcellular fractionation, EMSA, Western blot, pharmacological inhibition (cyclosporin A, PMA, ionomycin, EGTA) Molecular and cellular biology High 8668212
2000 p38 MAPK phosphorylates NFATp in vitro and interacts with NFATp in vivo; activation of p38 (via MKK6) counteracts calcium-induced nuclear accumulation of NFATp (but not NFATc) and inhibits NFATp-driven transcription; p38-mediated nuclear export of NFATp is CRM1-dependent (Leptomycin B-sensitive). In vitro kinase assay, co-immunoprecipitation, cotransfection with activated MKK6/p38, nuclear/cytoplasmic fractionation, Leptomycin B treatment The Journal of biological chemistry High 10788511
2003 Crystal structure of NFAT1 (NFATC2) bound as a dimer to the HIV-1 LTR κB element reveals a novel asymmetric dimerization mode through the C-terminal Rel homology subdomain, distinct from other Rel family dimers; both N- and C-terminal subdomains form protein-protein contacts encircling the DNA. X-ray crystallography Nature structural biology High 12949493
1998 NFAT1 induces cooperative DNA bending at the ARRE2 site in the NFAT1-Fos-Jun ternary complex that differs from the sum of individual bends; NFAT1 interaction with the Fos-Jun leucine zipper (specifically three N-terminal residues) can reverse the orientation of Fos-Jun heterodimer binding on DNA. Gel electrophoretic phasing analysis, fluorescence resonance energy transfer (FRET) orientation assay, mutagenesis of Fos/Jun leucine zippers Proceedings of the National Academy of Sciences of the United States of America High 9653115
2008 NFATp dimerization on the TNF promoter NFAT-bZIP element creates a dimer-specific function: the NFATp dimer and its bZIP partner bind noncooperatively to this element, whereas a monomer recruits bZIP cooperatively; NFATp dimer-specific activation subdomains interact with the coactivator CBP and are required for transcriptional activation from the TNF element. Consensus binding site determination, DNase footprinting, transcriptional reporter assays, coactivator interaction assays Proceedings of the National Academy of Sciences of the United States of America High 19060202
2001 NFATC2 is required intrinsically for skeletal muscle cell growth: NFATC2-null primary myotubes show reduced size and myonuclear number; retroviral re-expression of NFATC2 rescues these defects; NFATC2 controls a second phase of myoblast fusion (nuclear accretion) after initial myotube formation. NFATC2 knockout mouse analysis, primary muscle cell culture, retroviral rescue, morphometric measurement of myotube size and nuclear number The Journal of cell biology High 11309414
2003 Prostaglandin F2α (PGF2α) stimulates skeletal muscle cell growth through the FP receptor and requires NFATC2 activation: PGF2α activates NFAT, and NFATC2-null myotubes fail to grow or accrue nuclei in response to PGF2α, identifying the first intersection between prostaglandin receptor signaling and NFAT. PGF2α/analogue treatment of primary muscle cultures, NFAT reporter assay, NFATC2 knockout myotubes, nuclear accretion counts The Journal of cell biology High 12695501
2000 NFATp (NFATC2) functions as a repressor of chondrogenesis in vivo: mice lacking NFATp spontaneously develop cartilage from extraarticular connective tissue, and NFATp overexpression in cartilage cell lines extinguishes the cartilage phenotype; NFATp expression is regulated during mesenchymal stem cell chondrogenic differentiation. NFATp knockout mouse histology, overexpression in chondrocyte cell lines, cartilage marker expression analysis The Journal of experimental medicine High 10620601
2002 NFATc2 negatively regulates CDK4 expression by binding a canonical NFAT site in the CDK4 promoter in a calcium-sensitive, FK506/CsA-sensitive, and histone deacetylase-sensitive manner; ectopic NFATc2 inhibits CDK4 promoter activity; calcineurin Aα−/− and NFATc2−/− mice have elevated CDK4 protein levels. Promoter-reporter assays, pharmacological inhibition (FK506, CsA, HDAC inhibitors), NFATc2 overexpression, Western blot of CDK4 in KO mice Molecular cell High 12453415
2002 IL-6 upregulates NFATc2 protein levels in CD4+ T cells, increasing NFAT transcriptional activity, which drives IL-4 production; CD4+ T cells lacking NFATc2 fail to produce IL-4 in response to IL-6, preventing Th2 differentiation. NFATc2 knockout CD4+ T cells, IL-6 stimulation, IL-4 ELISA, NFAT transcriptional reporter, cyclosporin A inhibition The Journal of experimental medicine High 12093869
2002 NFAT1 (NFATc2) and NFAT2 are both positive regulators of IL-4 gene transcription when constitutively active (Ala substitution) forms are expressed; the disparate knockout phenotypes reflect differential regulation of the two proteins rather than intrinsic differences in DNA binding or transcriptional activity at the IL-4 locus. Constitutively active (phospho-Ser→Ala) mutant NFAT overexpression, IL-4 reporter and secretion assays European journal of immunology Medium 12355451
2005 NFATc2 directly binds the IL-21 proximal promoter and activates its transcription in Th2 cells; T-bet represses IL-21 transcription in Th1 cells by inhibiting NFATc2 binding to the IL-21 promoter. Promoter-reporter assays, chromatin immunoprecipitation (ChIP), EMSA, T-bet overexpression/NFATc2 competition Proceedings of the National Academy of Sciences of the United States of America High 15684054
2009 GSK-3β mediates inhibition of NFAT (including NFAT1) activity downstream of Akt1; GSK-3β-dependent NFAT inhibition leads to proteasomal degradation of NFAT and blocks breast cancer cell migration; GSK-3β mutants unresponsive to Akt reveal that Akt-mediated inhibition of migration is mediated through GSK-3β. GSK-3β shRNA and selective inhibitor, GSK-3β mutants unresponsive to Akt, NFAT reporter, proteasome inhibitor assays, migration assay Molecular cancer research Medium 19258413
2011 NFATc2 in pancreatic cancer cells targets the p15(INK4b) promoter and induces heterochromatin formation through sequential recruitment of histone methyltransferase Suv39H1, H3K9 trimethylation, and HP1γ docking; inactivation of NFATc2 disrupts this repressor complex, restoring p15(INK4b) expression and inhibiting cancer growth. ChIP, co-immunoprecipitation, DNA pulldown, reporter assays, xenograft tumor models, H3K9me3 ChIP Gastroenterology High 22079596
2012 NFAT1 (NFATC2) directly binds the mdm2 P2 promoter in vitro and in vivo and upregulates MDM2 transcription; enforced NFAT1 expression elevates MDM2 protein and reduces p53 function after DNA damage. EMSA, ChIP, reporter assays, NFAT1 overexpression, Western blot The Journal of biological chemistry High 22787160
2012 VRK2 directly interacts with and phosphorylates NFAT1 at Ser-32 within its N-terminal transactivation domain; this phosphorylation by VRK2 increases NFAT1-dependent transcription and COX-2 expression through the NFAT1 binding site in the COX-2 promoter, promoting tumor cell invasion. In vitro kinase assay, co-immunoprecipitation, luciferase reporter with COX-2 promoter, VRK2 RNAi, invasion assay The Journal of biological chemistry High 23105117
2016 LRRK2 kinase selectively phosphorylates NFATc2 and induces its nuclear translocation in microglia; α-synuclein activates LRRK2, which phosphorylates NFATc2 to drive neuroinflammatory TNF-α and IL-6 expression; genetic or pharmacological LRRK2 inhibition reduces NFATc2 nuclear translocation and microglial neurotoxicity. Primary mouse microglia cultures, LRRK2 genetic knockout/pharmacological inhibition, nuclear fractionation, cytokine ELISA, in vivo synucleinopathy mouse model Science translational medicine High 33055242
2016 GSK-3β phosphorylates NFATc2 at SP2 motif to stabilize NFATc2 protein in the nucleus of pancreatic cancer cells; additionally, GSK-3β maintains NFATc2 activation through stabilization of NFATc2-STAT3 complexes via GSK-3β-mediated STAT3 phosphorylation at Y705, stimulating euchromatin formation at NFATc2 target promoters such as CDK6. Co-immunoprecipitation, ChIP, reporter assay, GSK-3β inhibition/activation, xenograft and GEMM models Molecular cancer therapeutics High 26823495
2016 NFAT1 (NFATC2) directly regulates IL8 and MMP3 transcription in melanoma cells to promote tumor growth and lung metastasis; silencing NFAT1 reduces IL8 and MMP3 expression, and restoration rescues expression to baseline; both genes are validated as direct transcriptional targets by rescue experiments. NFAT1 stable silencing, microarray, qRT-PCR, overexpression rescue, in vivo xenograft/metastasis assay Cancer research Medium 27013197
2010 NFATc2 directly binds two NFAT-binding sites in the 5'-flanking region of the mouse Ccr9 gene and cooperates with the RAR/RXR complex bound to an adjacent RA response element half-site to drive CCR9 expression; NFATc2 enhances RARα binding to the RA response element; NFATc1, though it also binds the same sites and RARα/RXRα, inhibits NFATc2-dependent promoter activity. Reporter assays, DNA-affinity precipitation, direct protein interaction assay, murine naive CD4+ T cells, cyclosporin A inhibition Journal of immunology High 21148038
2021 NFATC2 induces β cell proliferation and activates ~2200 transcriptional targets in human islets; NFATC2 response elements in the SOX2 3' enhancer and ALDH1A1 5' enhancer are identified; NFATC2 induces Nr4a1, which is required for much of the proliferative effect; FOXP family transcription factors cooperate with NFATC2 to regulate β cell proliferation. Active NFATC2 expression in human islets, RNA-seq, ChIP-seq, FOXP1/2/4 triple KO islets, Nr4a1 deletion, ATAC-seq The Journal of clinical investigation High 34491912
2014 NFATc2 mediates epigenetic modification of DC cytokine and chemokine gene loci in response to dectin-1 stimulation; genome-wide NFATc2 binding (ChIP-seq) reveals occupancy at cytokine/chemokine loci, and NFATc2 binding is required to induce the H3K4me3 activating histone mark at these loci. ChIP-seq for NFATc2 genome-wide binding, H3K4me3 ChIP, gene expression profiling, dectin-1 stimulation of DCs Nucleic acids research High 25550437
2022 Dapl1 restrains NFATc2 activation in CD8+ T cells; Dapl1 deficiency enhances NFATc2 activation, improving effector function and preventing exhaustion; exhausted CD8+ T cells display attenuated NFATc2 activation due to Tim3-mediated feedback inhibition, which Dapl1 deletion rescues. Dapl1 KO mice, T cell adoptive transfer, NFATc2 reporter/activation assay, Tim3 feedback inhibition analysis, tumor models Nature cell biology High 35773432
2017 NFATc2 binds the 3' enhancer region of SOX2, coupling NFATc2/SOX2 to upregulate ALDH1A1 via its 5' enhancer; this NFATc2/SOX2/ALDH1A1 axis attenuates oxidative stress from cancer drug treatment, promoting drug resistance in lung cancer tumor-initiating cells. NFATc2 KD/OE, reporter assays, ChIP for NFATc2 binding to SOX2 and ALDH1A1 enhancers, sphere formation and in vivo tumorigenesis assays eLife Medium 28737489
2020 NFAT1 directly binds the MMP-9 promoter in melanoma cells and drives MMP-9 expression; CD147 activates NFAT1 via the intracellular Ca2+-calcineurin pathway; knockdown of NFAT1 suppresses melanoma metastasis in an NFAT1-dependent manner; CD147 knockdown reduces NFAT1-MMP-9 promoter binding. Luciferase reporter with MMP-9 promoter, ChIP for NFAT1 at MMP-9 promoter, siRNA knockdown, Ca2+ signaling assays Pigment cell & melanoma research Medium 32339381
2021 FGF19/FGFR4 signaling activates store-operated Ca2+ entry (SOCE) via PLCγ and ERK1/2 pathways, which activates calcineurin and promotes NFATc2 nuclear translocation; nuclear NFATc2 transcriptionally activates stemness genes (NANOG, OCT4, SOX2) and FGF19 itself, creating a positive feedback loop sustaining liver cancer stem cell self-renewal. Ca2+ imaging, calcineurin activity assay, NFATc2 nuclear fractionation, ChIP for NFATc2 at stemness gene promoters, sphere assays, FGFR4 knockdown/overexpression Theranostics Medium 33754043
2016 NFAT1 (NFATc2) directly binds to and activates the IL8 gene promoter in breast cancer cells, leading to IL8 secretion that promotes primary human neutrophil migration; NFAT1-mediated IL8 production is stimulated by thapsigargin and suppresses nascent tumor growth by a non-cell-autonomous mechanism. ChIP for NFAT1 at IL8 promoter, NFAT reporter, thapsigargin stimulation, neutrophil migration assay, xenograft tumor growth Molecular oncology Medium 25735562
2015 NFATc2 controls melanoma dedifferentiation by inducing expression of membrane-bound TNF-α (mTNF-α), which then regulates a c-Myc–Brn2 axis to suppress MITF and maintain a dedifferentiated state; NFATc2 silencing upregulates MITF, melanocyte differentiation antigens, and pigmentation. siRNA and shRNA silencing, NFATc2 inhibitor, TNF-α neutralization, c-Myc inhibition, Brn2 silencing, FACS, cytolytic T cell assay Oncogene Medium 26387540
2022 NFAT1 is upregulated in spinal microglia after nerve ligation via TET2-mediated DNA demethylation; NFAT1 directly binds promoters of Itgam, Tnf, Il-1b, and c-Myc in the spinal cord; NFAT1 promotes microglial proliferation through c-MYC; microglia-specific deletion of Nfat1 attenuates neuropathic pain. Microglia-specific Nfat1 KO mice, ChIP for NFAT1 binding, c-MYC overexpression, intrathecal siRNA injection, TET2/DNA methylation analysis Advanced science Medium 35892263
2012 NFAT1 physically interacts with Stat5 through Stat5's DNA-binding and transactivation domains; ectopic NFAT1 inhibits Stat5 transactivation, Stat5-mediated transcription, and Stat5a binding to its target promoter; conversely, Stat5 inhibits NFAT1 signaling, establishing mutual negative cross-talk. Co-immunoprecipitation, luciferase reporter, ChIP for Stat5a, NFAT1 overexpression and RNAi, VIVIT (NFAT inhibitor) treatment Molecular endocrinology Medium 21964595
2006 NFAT1 is required for B cell clonal anergy: NFAT1-deficient mice crossed with anti-lysozyme Ig transgenic/soluble lysozyme double transgenic mice show relief of B cell anergy, demonstrating that NFAT1 mediates peripheral B cell tolerance to self-antigen. NFAT1 KO mice crossed with double-transgenic anergy model, serum antibody levels, B cell numbers, proliferation assays Journal of immunology Medium 16849457
2012 NFAT1 mediates the induction of anergy-associated genes in CD4+ T cells in response to cancer antigen stimulation without costimulation; NFAT1-deficient antigen-specific CD4+ T cells show blunted anergy induction and enhanced anti-tumor responses in a murine melanoma model. NFAT1 KO mouse melanoma model, antigen-specific CD4+ T cell cytokine assays, NFAT1-deficient T cell transfer Cancer research Medium 22865456
2016 NFATc2 and NFKB1/RELA directly bind a core regulatory element (CRE, -540/-80 bp from TSS) in the Ets1 promoter to trans-activate Ets1 transcription in metastatic breast cancer cells; CRISPR/Cas9 deletion of the CRE reduces Ets1 expression and tumor invasiveness-related gene programs. ChIP for NFATc2 and NFKB1/RELA at Ets1 CRE, EMSA, CRISPR/Cas9 CRE deletion, reporter assays Oncogenesis Medium 30467308
2004 IL-15 specifically recruits NFAT1 (but not NFAT2) to the κB-like NFAT site in the CX3CR1 promoter to repress CX3CR1 expression, while IL-2 recruits NFAT2 to activate CX3CR1; NFAT1-deficient mice fail to show IL-15-dependent CX3CR1 downregulation. ChIP for NFAT1/NFAT2 at CX3CR1 promoter, NFAT1 KO mice, NFAT inhibitors (CsA, VIVIT), mutation of κB-NFAT site, reporter assays The Journal of biological chemistry High 15347678

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun. Nature 715 8397339
1993 Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science (New York, N.Y.) 423 8235597
1996 Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity 376 8612134
1995 Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. Molecular and cellular biology 316 7565732
1996 Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity. The Journal of biological chemistry 253 8631904
1996 Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2/Jun and NFATp. Molecular and cellular biology 219 8552071
2001 Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway. The Journal of cell biology 206 11309414
2000 The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis. The Journal of experimental medicine 163 10620601
1996 Cell-type-specific regulation of the human tumor necrosis factor alpha gene in B cells and T cells by NFATp and ATF-2/JUN. Molecular and cellular biology 161 8816436
2002 Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation. The Journal of experimental medicine 150 12093869
2002 NFATc2-mediated repression of cyclin-dependent kinase 4 expression. Molecular cell 144 12453415
1994 The role of NFATp in cyclosporin A-sensitive tumor necrosis factor-alpha gene transcription. The Journal of biological chemistry 124 7982959
1995 Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding. The Journal of experimental medicine 123 7650486
2003 Prostaglandin F2(alpha) stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway. The Journal of cell biology 119 12695501
2000 A role for the p38 MAP kinase pathway in the nuclear shuttling of NFATp. The Journal of biological chemistry 117 10788511
2001 NFATc2 and NFATc3 regulate T(H)2 differentiation and modulate TCR-responsiveness of naïve T(H)cells. Nature immunology 115 11740499
1995 Human granulocyte-macrophage colony-stimulating factor enhancer function is associated with cooperative interactions between AP-1 and NFATp/c. Molecular and cellular biology 114 7891702
1994 Expression of the transcription factor NFATp in a neuronal cell line and in the murine nervous system. The Journal of biological chemistry 114 7961754
2009 RAGE regulates BACE1 and Abeta generation via NFAT1 activation in Alzheimer's disease animal model. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 109 19332646
2002 NFAT1 and NFAT2 are positive regulators of IL-4 gene transcription. European journal of immunology 105 12355451
1995 Direct demonstration of NFATp dephosphorylation and nuclear localization in activated HT-2 cells using a specific NFATp polyclonal antibody. The Journal of biological chemistry 105 7545680
1996 T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1. Molecular and cellular biology 101 8668212
1996 Identification of a physical interaction between calcineurin and nuclear factor of activated T cells (NFATp). The Journal of biological chemistry 89 8576111
2003 Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element. Nature structural biology 87 12949493
2016 NFAT1 Directly Regulates IL8 and MMP3 to Promote Melanoma Tumor Growth and Metastasis. Cancer research 83 27013197
2012 Galectin-3 contributes to melanoma growth and metastasis via regulation of NFAT1 and autotaxin. Cancer research 83 22986745
1995 Phosphorylation of the transcription factor NFATp inhibits its DNA binding activity in cyclosporin A-treated human B and T cells. The Journal of biological chemistry 83 7657645
2011 Restricted heterochromatin formation links NFATc2 repressor activity with growth promotion in pancreatic cancer. Gastroenterology 77 22079596
2019 EWSR1/FUS-NFATc2 rearranged round cell sarcoma: clinicopathological series of 4 cases and literature review. Human pathology 76 31078563
2017 Regulator of Calcineurin 1 Gene Isoform 4, Down-regulated in Hepatocellular Carcinoma, Prevents Proliferation, Migration, and Invasive Activity of Cancer Cells and Metastasis of Orthotopic Tumors by Inhibiting Nuclear Translocation of NFAT1. Gastroenterology 74 28583823
2011 Nfat1 regulates adult articular chondrocyte function through its age-dependent expression mediated by epigenetic histone methylation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 73 21452283
2015 Genome-wide analysis links NFATC2 with asparaginase hypersensitivity. Blood 70 25987655
2020 LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies. Science translational medicine 68 33055242
2005 NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression. Proceedings of the National Academy of Sciences of the United States of America 68 15684054
2013 NFATc1 and NFATc2 repress spontaneous osteoarthritis. Proceedings of the National Academy of Sciences of the United States of America 67 24248346
2009 microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells. Blood 67 19286996
2009 Akt/protein kinase b and glycogen synthase kinase-3beta signaling pathway regulates cell migration through the NFAT1 transcription factor. Molecular cancer research : MCR 65 19258413
2020 NKX3-1 Is a Useful Immunohistochemical Marker of EWSR1-NFATC2 Sarcoma and Mesenchymal Chondrosarcoma. The American journal of surgical pathology 64 31972596
1999 A two-hit mechanism for vitamin D3-mediated transcriptional repression of the granulocyte-macrophage colony-stimulating factor gene: vitamin D receptor competes for DNA binding with NFAT1 and stabilizes c-Jun. Molecular and cellular biology 64 10330159
1995 Only one of the two DNA-bound orientations of AP-1 found in solution cooperates with NFATp. Current biology : CB 63 7583146
2003 Cell fusion in skeletal muscle--central role of NFATC2 in regulating muscle cell size. Cell cycle (Georgetown, Tex.) 62 12963831
1995 NFATp, a cyclosporin-sensitive transcription factor implicated in cytokine gene induction. Journal of leukocyte biology 61 7722411
2019 DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma. Journal of cancer research and clinical oncology 60 30895378
2019 EWSR1-NFATC2 and FUS-NFATC2 Gene Fusion-Associated Mesenchymal Tumors: Clinicopathologic Correlation and Literature Review. Sarcoma 57 31049020
2005 NFAT5 binds to the TNF promoter distinctly from NFATp, c, 3 and 4, and activates TNF transcription during hypertonic stress alone. Nucleic acids research 57 16027109
2023 Gsmtx4 Alleviated Osteoarthritis through Piezo1/Calcineurin/NFAT1 Signaling Axis under Excessive Mechanical Strain. International journal of molecular sciences 56 36835440
2013 NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells. PloS one 54 23762456
2012 Transcription factor NFAT1 activates the mdm2 oncogene independent of p53. The Journal of biological chemistry 54 22787160
2017 NFAT1-regulated IL6 signalling contributes to aggressive phenotypes of glioma. Cell communication and signaling : CCS 53 29258522
2010 Retinoic acid-induced CCR9 expression requires transient TCR stimulation and cooperativity between NFATc2 and the retinoic acid receptor/retinoid X receptor complex. Journal of immunology (Baltimore, Md. : 1950) 52 21148038
2018 Discovery and Characterization of Dual Inhibitors of MDM2 and NFAT1 for Pancreatic Cancer Therapy. Cancer research 51 30217928
2017 NFATc2 enhances tumor-initiating phenotypes through the NFATc2/SOX2/ALDH axis in lung adenocarcinoma. eLife 51 28737489
2012 Kaposi's sarcoma herpesvirus K15 protein contributes to virus-induced angiogenesis by recruiting PLCγ1 and activating NFAT1-dependent RCAN1 expression. PLoS pathogens 50 23028325
2020 FUS-NFATC2 or EWSR1-NFATC2 Fusions Are Present in a Large Proportion of Simple Bone Cysts. The American journal of surgical pathology 49 32991339
2018 EWSR1-NFATC2 gene fusion in a soft tissue tumor with epithelioid round cell morphology and abundant stroma: a case report and review of the literature. Human pathology 49 29626598
2018 Upregulation of Ets1 expression by NFATc2 and NFKB1/RELA promotes breast cancer cell invasiveness. Oncogenesis 49 30467308
2019 MDM2-NFAT1 dual inhibitor, MA242: Effective against hepatocellular carcinoma, independent of p53. Cancer letters 46 31181320
2022 NFAT1 Orchestrates Spinal Microglial Transcription and Promotes Microglial Proliferation via c-MYC Contributing to Nerve Injury-Induced Neuropathic Pain. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 42 35892263
2012 NFATc2 is a potential therapeutic target in human melanoma. The Journal of investigative dermatology 42 22718120
2016 GSK-3β Governs Inflammation-Induced NFATc2 Signaling Hubs to Promote Pancreatic Cancer Progression. Molecular cancer therapeutics 41 26823495
2012 Human VRK2 (vaccinia-related kinase 2) modulates tumor cell invasion by hyperactivation of NFAT1 and expression of cyclooxygenase-2. The Journal of biological chemistry 41 23105117
2021 FGF19/SOCE/NFATc2 signaling circuit facilitates the self-renewal of liver cancer stem cells. Theranostics 39 33754043
2015 NFAT1 promotes intratumoral neutrophil infiltration by regulating IL8 expression in breast cancer. Molecular oncology 39 25735562
2015 NFATc2 is an intrinsic regulator of melanoma dedifferentiation. Oncogene 39 26387540
2019 An actionable axis linking NFATc2 to EZH2 controls the EMT-like program of melanoma cells. Oncogene 37 30710146
2019 NFAT1-Mediated Regulation of NDEL1 Promotes Growth and Invasion of Glioma Stem-like Cells. Cancer research 36 30940662
2022 A novel FBW7/NFAT1 axis regulates cancer immunity in sunitinib-resistant renal cancer by inducing PD-L1 expression. Journal of experimental & clinical cancer research : CR 35 35081978
2021 Identification of EWSR1-NFATC2 fusion in simple bone cysts. Histopathology 35 33316098
2013 The transcription factor NFAT1 induces apoptosis through cooperation with Ras/Raf/MEK/ERK pathway and upregulation of TNF-α expression. Biochimica et biophysica acta 35 23583303
2020 PDGF mediates pulmonary arterial smooth muscle cell proliferation and migration by regulating NFATc2. Molecular medicine reports 34 33179105
1998 Molecular basis of cooperative DNA bending and oriented heterodimer binding in the NFAT1-Fos-Jun-ARRE2 complex. Proceedings of the National Academy of Sciences of the United States of America 34 9653115
2004 Interleukin (IL)-15 and IL-2 reciprocally regulate expression of the chemokine receptor CX3CR1 through selective NFAT1- and NFAT2-dependent mechanisms. The Journal of biological chemistry 33 15347678
2002 Identification of three NFAT binding motifs in the 5'-upstream region of the human CD3gamma gene that differentially bind NFATc1, NFATc2, and NF-kappa B p50. The Journal of biological chemistry 33 12374807
2022 Dapl1 controls NFATc2 activation to regulate CD8+ T cell exhaustion and responses in chronic infection and cancer. Nature cell biology 32 35773432
2019 miR-454-3p exerts tumor-suppressive functions by down-regulation of NFATc2 in glioblastoma. Gene 32 31181312
2012 NFAT1 supports tumor-induced anergy of CD4(+) T cells. Cancer research 32 22865456
2021 TRPC3 promotes tumorigenesis of gastric cancer via the CNB2/GSK3β/NFATc2 signaling pathway. Cancer letters 30 34311033
1995 Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp. Cytogenetics and cell genetics 30 7842733
2015 NFAT1 deficit and NFAT2 deficit attenuate EAE via different mechanisms. European journal of immunology 29 25630465
2021 Propofol maintains Th17/Treg cell balance and reduces inflammation in rats with traumatic brain injury via the miR‑145‑3p/NFATc2/NF‑κB axis. International journal of molecular medicine 28 34036377
2020 LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 32537408
2024 An NFAT1-C3a-C3aR Positive Feedback Loop in Tumor-Associated Macrophages Promotes a Glioma Stem Cell Malignant Phenotype. Cancer immunology research 27 38289255
2020 Testicular Lmcd1 regulates phagocytosis by Sertoli cells through modulation of NFAT1/Txlna signaling pathway. Aging cell 26 32840323
2015 Inhibiting NFAT1 for breast cancer therapy: New insights into the mechanism of action of MDM2 inhibitor JapA. Oncotarget 25 26461225
2022 SOCE-mediated NFAT1-NOX2-NLRP1 inflammasome involves in lipopolysaccharide-induced neuronal damage and Aβ generation. Molecular neurobiology 24 35286582
2006 Involvement of NFAT1 in B cell self-tolerance. Journal of immunology (Baltimore, Md. : 1950) 24 16849457
2021 Identification of direct transcriptional targets of NFATC2 that promote β cell proliferation. The Journal of clinical investigation 23 34491912
2016 FOXP1 enhances tumor cell migration by repression of NFAT1 transcriptional activity in MDA-MB-231 cells. Cell biology international 23 27859969
2014 NFATc2 mediates epigenetic modification of dendritic cell cytokine and chemokine responses to dectin-1 stimulation. Nucleic acids research 23 25550437
2008 A dimer-specific function of the transcription factor NFATp. Proceedings of the National Academy of Sciences of the United States of America 23 19060202
2024 The RNA m6A reader IGF2BP3 regulates NFAT1/IRF1 axis-mediated anti-tumor activity in gastric cancer. Cell death & disease 22 38448411
2021 LRRK2-NFATc2 Pathway Associated with Neuroinflammation May Be a Potential Therapeutic Target for Parkinson's Disease. Journal of inflammation research 22 34168481
2019 NFAT1 and NFAT2 Differentially Regulate CTL Differentiation Upon Acute Viral Infection. Frontiers in immunology 22 30828328
2011 Negative cross talk between NFAT1 and Stat5 signaling in breast cancer. Molecular endocrinology (Baltimore, Md.) 21 21964595
2018 Invasion and migration of MDA-MB-231 cells are inhibited by block of AhR and NFAT: role of AhR/NFAT1/β4 integrin signaling. Journal of applied toxicology : JAT 20 30294794
2018 Activation of Th2 cells downregulates CRTh2 through an NFAT1 mediated mechanism. PloS one 19 29969451
2020 OSW-1 inhibits tumor growth and metastasis by NFATc2 on triple-negative breast cancer. Cancer medicine 18 32515123
2020 CD147 regulates melanoma metastasis via the NFAT1-MMP-9 pathway. Pigment cell & melanoma research 17 32339381
2016 NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes. Cell cycle (Georgetown, Tex.) 17 27399331
2012 NFAT1 C-terminal domains are necessary but not sufficient for inducing cell death. PloS one 17 23110116

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