| 1999 |
NFATc4 (NF-ATc4/NF-AT3) in hippocampal neurons translocates from cytoplasm to nucleus and activates NF-AT-dependent transcription in response to electrical activity or potassium depolarization. This calcineurin-mediated nuclear translocation is critically dependent on calcium entry through L-type voltage-gated calcium channels. GSK-3 phosphorylates NFATc4, promoting its nuclear export and antagonizing NFATc4-dependent transcription. |
Neuronal activity/K+ depolarization assays, pharmacological inhibition of calcineurin and L-type Ca2+ channels, GSK-3 phosphorylation assays, reporter gene assays, nuclear translocation imaging |
Nature |
High |
10537109
|
| 2002 |
NFATc4 is phosphorylated by p38 MAP kinase at multiple residues including Ser168 and Ser170 within the NFAT homology domain. Replacement of Ser168,170 with Ala promotes nuclear localization of NFATc4 and increases NFAT-mediated transcription activity. NFATc4 is not phosphorylated by JNK. Constitutively nuclear NFATc4 (Ala168,170 mutant) promotes adipocyte differentiation via upregulation of PPARγ2, which is identified as a transcriptional target of NFAT. |
In vitro phosphorylation assays, site-directed mutagenesis, reporter assays, stable cell line expression, adipocyte differentiation assays, promoter analysis |
Molecular and cellular biology |
High |
11997522
|
| 2001 |
NFATc4 contains two transactivation domains at the NH2 and COOH termini, each interacting with distinct regions of the coactivator CBP (KIX and CH3 domains respectively). Both transactivation domains are required for CBP-mediated potentiation of NFATc4 transcription; removal of either domain abolishes CBP potentiation. |
Co-immunoprecipitation, deletion mutagenesis, reporter assays, in vitro binding assays |
The Journal of biological chemistry |
High |
11514544
|
| 2000 |
In cardiac myocytes, Ras (but not Rac1, RhoA, or Cdc42) stimulates NFAT3 nuclear translocation and transcriptional activity via a calcineurin-dependent mechanism involving the MEK1/c-Raf/ERK2 pathway. Dominant-negative Ras blocks phenylephrine-stimulated NFAT3 activation and calcineurin activity. Cyclosporin A blocks V12ras-stimulated NFAT transcription, placing Ras upstream of calcineurin. |
Expression of constitutively active and dominant-negative Ras/GTPase mutants, reporter assays, NFAT3 nuclear localization imaging, calcineurin activity assays, pharmacological inhibitors |
The Journal of biological chemistry |
High |
11044444
|
| 2000 |
In cardiomyocytes stimulated by electrical pacing, calcineurin-mediated dephosphorylation of NFAT3 allows its translocation to the nucleus where it directly participates in activation of the Adss1 gene. Mutational analysis of the Adss1 5'-flanking region shows an NFAT binding site is essential for this activation. |
Electrical pacing of neonatal cardiomyocytes, calcineurin dephosphorylation assay, nuclear translocation assay, promoter mutational analysis, reporter assays |
The Journal of biological chemistry |
Medium |
10636885
|
| 2002 |
Genetic disruption of NFATc4 does not impair cardiac hypertrophic growth; in contrast, NFATc3 knockout significantly reduces calcineurin transgene-induced and pressure overload-induced cardiac hypertrophy. This genetic evidence shows NFATc4 is dispensable for calcineurin-mediated cardiac hypertrophy while NFATc3 is required. |
Targeted gene disruption (knockout mice), cardiac hypertrophy models (calcineurin transgene, pressure overload, angiotensin II), morphometric analysis |
Molecular and cellular biology |
High |
12370307
|
| 2003 |
NFATc3 and NFATc4 are required for cardiac development; double knockout mice show embryonic lethality with thin ventricles, reduced cardiomyocyte proliferation, and defective mitochondrial function including reduced complex II and IV respiratory chain activity. Cardiac-specific expression of constitutively active NFATc4 in double-knockout embryos rescues ventricular myocyte proliferation, mitochondrial ultrastructure, and complex II enzyme activity, demonstrating NFATc4 is sufficient to support these functions. |
Double knockout mice, cardiac-specific rescue with constitutively active NFATc4 transgene, electron microscopy, enzymatic activity assays, histology |
Circulation research |
High |
12750314
|
| 2004 |
In hippocampal neurons, NFATc4 (NFAT3) accumulates in the nucleus under survival conditions (serum and high K+) and is exported under pro-apoptotic conditions. GSK3 inhibition by Li+ blocks NFATc4 nuclear export and promotes survival. RNA interference knockdown of NFAT3 induces apoptosis even under survival conditions, while constitutively active NFAT protects against apoptosis, demonstrating a pro-survival transcriptional function for NFAT3 in cerebellar granule neurons. |
Primary neuron culture, nuclear localization imaging, RNAi knockdown, Li+ pharmacology, apoptosis assays, constitutively active NFAT expression |
The Journal of biological chemistry |
High |
15537643
|
| 2005 |
NFATc4 (NFAT3) interacts with both ERα and ERβ in vitro and in mammalian cells in a ligand-independent manner, binding specifically to the ERβ activation function-1 domain. Overexpression of NFAT3 enhances ERα and ERβ transcriptional activities and upregulates downstream estrogen-responsive genes (pS2, cathepsin D). NFAT3 increases ERα binding to estrogen-responsive elements and is recruited to estrogen-responsive promoters. |
Yeast two-hybrid, GST pulldown, co-immunoprecipitation, ChIP, reporter assays, siRNA knockdown, gene expression analysis |
The Journal of biological chemistry |
High |
16219765
|
| 2005 |
RSK (p90 ribosomal S6 kinase) is recruited to the NFATc4-DNA transcription complex upon activation, demonstrated by DNA affinity isolation coupled with in-gel kinase assays. Bound RSK phosphorylates NFATc4 at Ser676, potentiating its DNA binding by increasing NFAT-DNA association. ERK MAP kinase interacts with NFATc4 at a distinct region from RSK. |
DNA affinity isolation, in-gel kinase assays, site-directed mutagenesis, phosphorylation assays, EMSA |
Molecular and cellular biology |
High |
15657420
|
| 2007 |
RSK2 directly interacts with NFATc4 (binding its NLS1, Ser/Pro repeat, and polyproline domains), phosphorylates NFATc4 in vitro (Km=3.559 μM), and induces nuclear localization of NFATc4 upon A23187 stimulation. RSK2-mediated activation of NFATc4 enhances its target gene promoter activity and promotes C2C12 myoblast differentiation into multinucleated myotubes. siRNA against RSK2, ERK1/2, or NFATc4 each inhibits myotube differentiation. |
Co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, nuclear localization imaging, reporter assays, C2C12 differentiation assay |
The Journal of biological chemistry |
High |
17213202
|
| 2008 |
mTOR phosphorylates Ser168,170 of endogenous NFATc4 (gate-keeping residues controlling subcellular distribution), acting as a basal kinase to maintain NFATc4 in the cytosol. ERK5 MAP kinase also mediates rephosphorylation of Ser168,170 for nuclear export, and phosphorylation by ERK5 primes subsequent phosphorylation by CK1α. Ablation of ERK5 in Erk5-/- cells shows defects in NFATc4 rephosphorylation and nucleocytoplasmic shuttling. |
Phospho-specific monoclonal antibody, kinetic phosphorylation analyses, Erk5 knockout cells, pharmacological inhibition, mutagenesis |
Molecular and cellular biology |
High |
18347059
|
| 2008 |
NFATc4 protein stability and transcriptional activity are regulated by ubiquitination via Lys48-linked polyubiquitin chains, leading to decreased protein levels. GSK3β activation enhances NFATc4 ubiquitination and decreases its transactivation, while GSK3β inhibition has opposite effects. Ubiquitination and GSK3β-induced phosphorylation together repress NFATc4-dependent cardiac-specific gene expression. |
Ubiquitination assays, Western blot, GSK3β activation/inhibition, reporter assays |
FEBS letters |
Medium |
19026640
|
| 2008 |
NFATc4 deafferentation-induced nuclear translocation and activation in AVCN neurons during a critical period is abolished by the calcineurin inhibitor FK506 and the NFAT-specific inhibitor 11R-VIVIT. NFATc4 activation mediates expression of FasL in cochlear nucleus, and NFAT inhibition attenuates deafferentation-induced apoptosis of AVCN neurons. |
In vivo cochlea removal, calcineurin inhibitor treatment, NFAT-specific peptide inhibitor (11R-VIVIT), immunostaining, apoptosis assays, FasL expression analysis |
The Journal of neuroscience |
Medium |
18354019
|
| 2009 |
NFATc4 (NFAT-3) directly occupies the GAP-43 promoter and acts as a transcriptional repressor of GAP-43 in neurons. Overexpression of NFAT-3 represses GAP-43 activation mediated by neurotrophin signaling. Endogenous NFAT-3 occupies the GAP-43 promoter in PC-12 cells, cultured neurons, and mouse brain as shown by ChIP. NFAT-3 is required to repress physiological GAP-43 expression in specific developmental windows in the mouse brain. |
ChIP assay, overexpression, reporter assays, cortical neuron culture, in vivo brain analysis |
The Journal of biological chemistry |
High |
19443652
|
| 2009 |
NFATc4 (NFAT isoform c4) activation by NMDAR stimulation in cortical neurons promotes antiapoptotic transcription, in part by regulating BDNF promoter IV transcription. NFATc4 knockdown reduces BDNF expression and induces cortical neuron apoptosis, while BDNF rescues from NFATc4 inhibition-induced apoptosis, establishing an NMDAR-NFATc4-BDNF pro-survival pathway. |
RNAi knockdown of NFATc4, NMDAR pharmacology, reporter assays (BDNF promoter IV), BDNF rescue experiment, apoptosis assays |
The Journal of neuroscience |
High |
19955386
|
| 2010 |
Lipin 1 represses NFATc4 transcriptional activity through direct protein-protein interaction. Both catalytically active and inactive lipin 1 suppress NFATc4 transcriptional activity, with suppression potentially involving recruitment of histone deacetylases to target promoters. Lipin 1 is present at the promoters of NFATc4 transcriptional targets (TNFα, resistin, FABP4, PPARγ) in vivo. |
Co-immunoprecipitation, reporter assays, ChIP assay, lipin-1 knockout mice, siRNA knockdown in 3T3-L1 adipocytes |
Molecular and cellular biology |
High |
20385772
|
| 2010 |
NFAT3 inhibits LCN2 (Lipocalin 2) gene expression and thereby reduces migration of ERα+ breast cancer cells. NFAT3 cooperates with ERα to inhibit migration but inhibits invasion independently. NFAT3 downregulation results in actin reorganization associated with increased migration and invasion. |
siRNA knockdown, invasion/migration assays, gene expression analysis, actin staining |
Oncogene |
Medium |
20101218
|
| 2011 |
FoxP1 physically interacts with Nfat3 (NFATc4) in cardiomyocytes; calcineurin activation induces FoxP1-Nfat3 complex formation visualized by bimolecular fluorescence complementation (BiFC). Amino acid substitutions at the predicted interaction interface inhibit complex formation. FoxP1 represses hypertrophy-associated genes (Myh7, Rcan1, Cx43, Anf, Bnp) and counteracts their activation by constitutively nuclear Nfat3. FoxP1 and Nfat3 co-occupy promoter regions of hypertrophy-associated genes in neonatal and adult heart tissue by ChIP. |
BiFC, co-immunoprecipitation, mutagenesis of interaction interface, reporter assays, ChIP, cardiomyocyte hypertrophy assays |
Molecular and cellular biology |
High |
21606195
|
| 2012 |
NFATc4 calcineurin-dependent activity is required selectively for survival of adult-born neurons in response to BDNF signaling in the mouse dentate gyrus. In NFATc4-/- mice, cyclosporin A injection and BDNF scavenger (TrkB-Fc) do not reduce adult-born neuron survival, whereas they do in wild-type mice. Absence of NFATc4 leads to selective defects in LTP and hippocampal-dependent spatial memory encoding. |
NFATc4 knockout mice, cyclosporin A injection, stereotaxic TrkB-Fc delivery, BrdU labeling/survival assays, LTP recording, spatial memory testing |
Proceedings of the National Academy of Sciences of the United States of America |
High |
22586092
|
| 2012 |
NFATc4 undergoes nuclear translocation only after prolonged (1-3 h) depolarization in neurons, in contrast to NFATc3 which translocates rapidly (~20 min). The serine-proline repeat region of NFATc4 is critical for determining the magnitude of NFATc4 nuclear localization. Knockdown of GSK3β significantly increases depolarization-induced NFATc4 nuclear localization. Inhibition of p38 or mTOR has no significant effect on NFATc4 nuclear import in neurons. |
NFATc3/NFATc4 chimera analysis, siRNA knockdown of GSK3β/p38/mTOR, live-cell imaging of nuclear translocation, phosphorylation assays in hippocampal and DRG neurons |
The Journal of biological chemistry |
High |
22977251
|
| 2013 |
NFAT3 (NFATc4) directly regulates miR-140 transcription by binding to the regulatory sequence of miR-140 (rsmiR-140). NFAT3 activation increases rsmiR-140 activity, and mutagenesis of NFAT binding sites in rsmiR-140 abolishes this activation. TGF-β interferes with NFAT3 translocation and subsequently decreases miR-140 expression. NFAT3 and SMAD3 directly regulate miR-140 independently of WWP2. |
siRNA silencing, luciferase reporter assays with mutagenesis, ChIP assay, immunocytochemistry |
Arthritis research & therapy |
Medium |
24257415
|
| 2014 |
NFATc4 is a transcriptional regulator of GABAA receptor subunits (GABRA2 and GABRA4) in hippocampal progenitor cells, regulating their expression via binding to specific promoter responsive elements as confirmed by ChIP and luciferase assays. GABAA receptor signaling modulates hippocampal neurogenesis through NFATc4 activity via calcineurin/NFATc4 axis. |
Genome-wide high-throughput study, ChIP assay, luciferase assays, calcineurin inhibitor treatment, NFATc4 knockout mice, neurogenesis quantification, behavioral assays |
The Journal of neuroscience |
High |
24948817
|
| 2015 |
NFAT3 directly binds to specific DNA sequences within the BACE1 promoter (confirmed by ChIP), increasing BACE1 promoter activity and transcription. Overexpression of NFAT3 increases BACE1 and Aβ production; disruption of NFAT3 decreases BACE1 gene transcription and protein expression. |
ChIP assay, reporter assays, overexpression, siRNA knockdown, Aβ measurement, transgenic APP/PS1 mice analysis |
Neurochemical research |
Medium |
25663301
|
| 2016 |
CDK3 (cyclin-dependent kinase 3) directly interacts with NFATc4 (NFAT3) and phosphorylates it at serine 259 (Ser259), enhancing its transactivation and transcriptional activity. The Ser259 phosphorylation is critical for EGF-stimulated cell transformation; mutation of NFAT3 at Ser259 reduces colony formation and xenograft tumor growth. |
Mammalian two-hybrid assay, in vitro kinase assay, site-directed mutagenesis (S259A), reporter assays, soft-agar colony formation, xenograft mouse model |
Oncogene |
High |
27893713
|
| 2016 |
NFATc4 interacts with myocardin to synergistically activate expression of the LTCC α1C (L-type Ca2+ channel α1C subunit) in cardiomyocytes. NFATc4 activates myocardin expression by binding to its promoter (confirmed by ChIP). Co-IP demonstrates direct NFATc4-myocardin interaction. |
Co-immunoprecipitation, ChIP assay, overexpression, siRNA knockdown, reporter assays, immunofluorescence, calcineurin inhibitor treatment |
Life sciences |
Medium |
27155398
|
| 2016 |
Neuritin elevates intracellular Ca2+ and increases Kv4.2 expression via the Ca2+/calcineurin/NFATc4 axis in cerebellar granule neurons. NFATc4 is recruited to the Kv4.2 gene promoter (confirmed by ChIP and luciferase reporter). Neuritin-induced nuclear accumulation of NFATc4 and consequent Kv4.2 expression/neuronal excitability changes are abrogated in Nfatc4-/- but not Nfatc2-/- mice. |
Nfatc4 knockout mice, calcineurin inhibitor, ChIP assay, luciferase reporter, Ca2+ imaging, AAV-mediated overexpression, patch-clamp |
The Journal of biological chemistry |
High |
27307045
|
| 2017 |
NFAT3 expression in T cells is regulated by TBX5; TBX5 binds to the NFAT3 promoter and its mutation diminishes NFAT3 promoter activity. NFAT3 in T cells suppresses IL-2 expression, while NFAT1 enhances it. The region of NFAT3 responsible for IL-2 promoter activity inhibition maps to the N-terminal transactivation domain, Ca2+-regulatory domain, and DNA-binding domain (identified by NFAT1/NFAT3 chimeric molecules). |
RNAi knockdown, reporter assays, NFAT1/NFAT3 chimeric molecules, promoter mutagenesis, TBX5 overexpression in T cells, chromatin accessibility analysis |
Journal of immunology |
Medium |
29180489
|
| 2018 |
BDNF regulates neurodevelopmental timing via sequestration of NFATc4 in Golgi (extranuclear compartment), preventing its transcriptional repressor activity. This leads to accelerated derepression of an NFI temporal occupancy gene program in cerebellar granule cells, including Bdnf itself, forming an autoregulatory loop. |
Subcellular fractionation/imaging of NFATc4-Golgi localization, NFI target gene expression analysis, BDNF treatment, cerebellar granule cell culture |
Molecular biology of the cell |
Medium |
29467254
|
| 2019 |
SIRT6 suppresses NFATc4 expression and activation in cardiomyocyte hypertrophy. SIRT6 overexpression represses NFATc4 protein/mRNA, elevates its phosphorylation, prevents nuclear accumulation, and suppresses BNP transcription. The catalytically inactive SIRT6 mutant (H133Y) does not show these effects, indicating dependence on deacetylase activity. SIRT6 physically interacts with NFATc4, suggesting SIRT6-mediated deacetylation of NFATc4. |
Adenovirus overexpression, plasmid transfection, catalytic mutant (H133Y), Western blot, immunofluorescence, siRNA rescue, co-immunoprecipitation |
Frontiers in pharmacology |
Medium |
30670969
|
| 2019 |
RCAN1.4 downregulation via DNMT1/DNMT3b-mediated promoter methylation in liver fibrosis leads to enhanced calcineurin/NFAT3 signaling and hepatic stellate cell activation. RCAN1.4 overexpression alleviates TGF-β1-induced liver fibrosis in a CaN/NFAT3 signaling-dependent manner. |
Bisulfite sequencing, ChIP assay (DNMT1/3b binding), rAAV8-RCAN1.4 overexpression in mice, siRNA knockdown, protein-protein interaction network analysis, liver fibrosis model |
Theranostics |
Medium |
31285763
|
| 2020 |
NFATc4 translocates from cytoplasm to nucleus in hepatocytes in NASH. Activated NFATc4 directly binds PPARα in the nucleus and negatively regulates its transcriptional activity, impairing hepatic fatty acid oxidation and increasing lipid deposition. NFATc4 activation increases osteopontin (OPN) production/secretion from hepatocytes, promoting macrophage-mediated inflammation and stellate cell fibrosis via paracrine signaling. |
Gain- and loss-of-function (NFATc4 overexpression/knockdown in mice and cells), nuclear fractionation, co-immunoprecipitation (NFATc4-PPARα interaction), NASH mouse model |
Journal of hepatology |
High |
32717288
|
| 2020 |
NFATC4 nuclear translocation is triggered by cisplatin treatment in ovarian cancer cells. NFATC4 activation induces G0 cell cycle arrest, decreased proliferation, and chemotherapy resistance. NFATC4 drives quiescence in part via downregulation of MYC. Inhibition of the NFATC4 pathway increases chemotherapy response. |
Nuclear translocation imaging, cell cycle analysis, proliferation assays, MYC expression analysis, gain- and loss-of-function, in vitro and in vivo xenograft models |
JCI insight |
Medium |
32182216
|
| 2020 |
NULP1 directly interacts with the topologically associating domain of NFAT3 via its C-terminal region (confirmed by co-immunoprecipitation), suppressing NFAT3 transcriptional activity. NULP1 knockout exacerbates aortic banding-induced cardiac hypertrophy while NULP1 transgenic overexpression blunts it. The NFAT pathway is identified as the downstream mechanism by VIVIT peptide rescue. |
Co-immunoprecipitation, Nulp1 knockout and transgenic mice, aortic banding, VIVIT peptide treatment, NFAT pathway screening, immunostaining |
Journal of the American Heart Association |
High |
32805187
|
| 2021 |
SIRT2-mediated deacetylation of NFATc4 inhibits its nuclear translocation and acetylation status in ethanol-exposed hepatocytes. NFATc4 overexpression impairs the negative regulation of RIPK3 and DAMPs release. SIRT2 knockdown abolishes the inhibitory effects of pterostilbene on NFATc4 nuclear translocation and acetylation, placing SIRT2 as an upstream regulator of NFATc4 acetylation. |
SIRT2 knockdown, NFATc4 overexpression, Western blot, immunofluorescence, acetylation status analysis, RIPK3/DAMP measurement |
Toxicology |
Medium |
34474091
|
| 2021 |
NFATc4 triggers hepatocyte senescence via repression of PPARγ. NFATc4 knockdown counteracts ethanol-induced hepatocyte senescence markers and protects against alcoholic liver injury. PPARγ deficiency abrogates the inhibitory effects of NFATc4 knockdown on hepatocyte senescence, oxidative stress, and steatosis, placing PPARγ downstream of NFATc4. |
siRNA knockdown, PPARγ knockdown epistasis, Western blot, immunofluorescence, senescence-associated β-galactosidase staining, in vivo mouse model |
Toxicology letters |
Medium |
34192554
|
| 2022 |
PPP3CA (calcineurin catalytic subunit) promotes dephosphorylation of NFATc4 and suppresses its phosphorylation, facilitating its nuclear translocation. CAMTA1 and PPP3CA competitively bind NFATc4; CAMTA1 knockdown promotes NFATc4 dephosphorylation (and resistance to oxaliplatin) in a PPP3CA-dependent manner. NFATc4 knockdown reverses oxaliplatin resistance caused by CAMTA1 knockdown, establishing a CAMTA1-PPP3CA-NFATc4 complex in colorectal cancer chemoresistance. |
Co-immunoprecipitation, competitive binding assay, siRNA knockdown epistasis, Western blot, xenograft mouse model |
Cell death discovery |
Medium |
35332122
|
| 2023 |
Calcineurin (Cn) dephosphorylates NFATC4 (identified by phosphoproteomics) to regulate aldosterone synthase (CYP11B2) expression and aldosterone production in adrenal zona glomerulosa. ZG-specific deletion of calcineurin subunit CnB1 diminishes Cyp11b2 expression and disrupts K+-mediated aldosterone synthesis. Deletion of NFATC4 impairs K+-dependent CYP11B2 stimulation, while constitutively active NFATC4 increases CYP11B2 expression. ChIP confirms NFATC4 directly regulates CYP11B2 promoter. |
Phosphoproteomics, ZG-specific CnB1 knockout, NFATC4 knockout, constitutively active NFATC4 expression, ChIP assay, calcineurin inhibitor (tacrolimus) in cell line and ex vivo adrenal tissue |
JCI insight |
High |
37310791
|
| 2024 |
Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, which facilitates alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. SRSF9 knockdown protects against TAC- or Mettl1-induced cardiac hypertrophy. |
Mettl1 knockout/cardiac-specific overexpression in mice, m7G modification assay, SRSF9 knockdown, alternative splicing analysis, TAC and Ang II models |
Advanced science |
Medium |
38810124
|
| 2024 |
NFATc4 knockout (but not NFATc3 knockout) increases RGC survival, improves retinal function, and delays axonal degeneration after optic nerve crush. NFATc4 is transiently upregulated and localizes to the ganglion cell layer after injury. Lentiviral re-delivery of NFATc4 to NFATc4-/- retinas reverses the pro-survival effect. NFATc4 knockout suppresses pro-apoptotic signaling (decreased cleaved caspase-3). |
NFATc4-/- and NFATc3-/- mice, optic nerve crush, lentiviral NFATc4 delivery rescue, microarray screening, immunostaining, retinal function testing |
Molecular neurobiology |
High |
38639863
|
| 2019 |
NFATc4 mediates expression of TNF and downstream hair cell apoptosis in the cochlea after ototoxic drug challenge. In Nfatc4-/- mice, hair cells show lower sensitivity to ototoxic damage and noise exposure, and the TNF-mediated apoptosis pathway is attenuated. NFATc4 is activated (nuclear translocation) in cochlear hair cells upon ototoxic challenge. |
Nfatc4-/- mice, ototoxic drug treatment, noise exposure, TNF and apoptosis pathway analysis, immunostaining |
Frontiers in immunology |
Medium |
31379853
|
| 2007 |
IL-18 suppresses adiponectin transcription via ERK1/2-dependent NFATc4 phosphorylation at Ser676 and NFATc4 nuclear translocation and in vivo DNA binding to the adiponectin promoter. IL-18 deletion or mutation of the NFATc4 core DNA-binding site in the adiponectin promoter-reporter reverses IL-18-mediated suppression. Inhibition of ERK1/2 attenuates NFATc4 Ser676 phosphorylation. |
Reporter assays with promoter mutation, ChIP (in vivo DNA binding), ERK inhibitors/siRNA, NFATc4 siRNA knockdown, nuclear translocation assay |
The Journal of biological chemistry |
High |
18086672
|
| 2004 |
NFATc4 forms a ternary transcriptional complex with Nishéd and co-activator p300 at an intronic regulatory element (IRE) of the MLC-2v gene in cardiomyocytes. This complex formation is enhanced by angiotensin II stimulation. Losartan (AT1 receptor antagonist) abolishes agonist-dependent IRE-complex interaction and MLC-2v transcription. |
Gel mobility shift assay (EMSA), co-immunoprecipitation, reporter assays, pharmacological inhibition |
The Journal of biological chemistry |
Medium |
15272022
|
| 2008 |
NFAT3 activity requires AP-1 co-binding for transcriptional activation; an NFAT3 promoter containing the NFAT core cis-element without an adjacent AP-1 binding site fails to show activation by H2O2 treatment. Dominant-negative c-Jun (TAM67) prevents H2O2 or ANG II from activating the NFAT3 promoter. ERK inhibition blocks AP-1 and NFAT3 activation. |
Promoter-luciferase reporter with AP-1 site mutations, dominant-negative c-Jun cotransfection, ERK pharmacological inhibition |
American journal of physiology. Cell physiology |
Medium |
17108007
|