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Ca(2+)-regulated transcription factor that is involved in several processes, including the development and function of the immune, cardiovascular, musculoskeletal, and nervous systems. Involved in T-cell activation, stimulating the transcription of cytokine genes, including that of IL2 and IL4. Along with NFATC3, involved in embryonic heart development. Involved in mitochondrial energy metabolism required for cardiac morphogenesis and function. Transactivates many genes involved in the cardiovascular system, including AGTR2, NPPB/BNP (in synergy with GATA4), NPPA/ANP/ANF and MYH7/beta-MHC. Involved in the regulation of adult hippocampal neurogenesis. Involved in BDNF-driven pro-survival signaling in hippocampal adult-born neurons. Involved in the formation of long-term spatial memory and long-term potentiation. In cochlear nucleus neurons, may play a role in deafferentation-induced apoptosis during the developmental critical period, when auditory neurons depend on afferent input for survival. Binds to and activates the BACE1/Beta-secretase 1 promoter, hence may regulate the proteolytic processing of the amyloid precursor protein (APP). Plays a role in adipocyte differentiation. May be involved in myoblast differentiation into myotubes. Binds the consensus DNA sequence 5'-GGAAAAT-3' (Probable). In the presence of CREBBP, activates TNF transcription. Binds to PPARG gene promoter and regulates its activity. Binds to PPARG and REG3G gene promoters.
基因功能參考文獻(xiàn):
TBX5 deficiency-mediated downregulation of NFAT3 is crucial for the high cytokine-producing activity of T cells PMID: 29180489
These results provided evidence supporting the oncogenic potential of NFAT3 and suggested that CDK3-mediated phosphorylation of NFAT3 has an important role in skin tumorigenesis. PMID: 27893713
Ca(2+)/calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) c4 axis is required for neuritin-induced Kv4.2 transcriptional expression and potentiation of IA densities in cerebellum granule neurons. PMID: 27307045
NFAT3 expression plays a role in regulating CXCR4 expression. PMID: 25514788
This is the first study to provide evidence of new and differential roles for NFAT3 and SMAD3 in the osteoarthritis process in the regulation of miR-140 transcription PMID: 24257415
Expression level of PPP3R1 and GATA4, and NFATC4 genes for transcription factors did not differ in studied subgroups of patients. PMID: 23888774
Syndecan-4 is essential for development of concentric myocardial hypertrophy via stretch-induced activation of the calcineurin-NFAT pathway PMID: 22164265
Dendritic spine loss and dendritic branching simplification induced by amyloid-beta peptide exposure are mimicked by constitutively active NFATC4, and abolished when NFATC4 activation is blocked by the genetically encoded inhibitor VIVIT. PMID: 22378890
Polymorphisms in the NFATc4 gene may confer certain protection or predisposition for new-onset diabetes after transplantation (NODAT). PMID: 22234350
These data suggest that the opposing transcriptional activities of FoxP1 and Nfat3 maintain cardiomyocyte homeostasis. PMID: 21606195
The expression of COX-2 was significantly associated with the expressions of transcription factors NFAT3 and c-Fos in nonsmall cell lung cancer. PMID: 21081043
an earlier unknown NFAT3/LCN2 axis that critically controls motility in breast cancer PMID: 20101218
Data show that inhibition of NFAT3 activation by shNFAT3 significantly downregulated tumor necrosis factor (TNF)-alpha induction, its receptor TNFR1, caspase 10, caspase 3, and poly (ADP-ribose) polymerase. PMID: 19784808
Polymorphism of the NFATC4 gene plays a role in the development of human cardiac hypertrophy. PMID: 12939651
NFAT3 may play a role in estrogen receptor signaling in breast cancer cells PMID: 16219765
This study demonstrates that silica was able to activate NFAT3 in an oxygen radical-dependent manner, which was required for TNF-alpha induction. PMID: 16489119
ionizing radiation is able to enhance cyclin D1 transcription induced by B[a]PDE, and NFAT3 is involved in the regulation of cyclin D1 transcription by B[a]PDE or B[a]PDE plus ionizing radiation PMID: 16645724
Neuronal nuclear translocation of NFAT requires a functional cytoskeleton. PMID: 17044076
overexpression of NFAT3 in cell lines originated from kidney decreased dose-dependently both ERalpha and ERbeta transcriptional activities in a ligand-independent manner. PMID: 17194453
RSK2 is an important kinase for NFAT3 in mediating myotube differentiation PMID: 17213202
Results provided direct evidence for the anti-oncogenic potential of the NFAT3 transcription factor. PMID: 17875713
Data show that the calcineurin pathway is activated in hypertrophic myocardium as demonstrated by increased calcineurin activity and expression of calcineurin A-beta and B, and GATA-4, and a shift of cytoplasmic NFAT-3 into the nucleus. PMID: 18034994
estrogen receptor may play a critical role in regulation of NFAT3 transcriptional activity PMID: 18668201
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亞細(xì)胞定位:
Cytoplasm, cytosol. Nucleus.
組織特異性:
Widely expressed, with high levels in placenta, lung, kidney, testis and ovary. Weakly expressed in spleen and thymus. In the hippocampus, expressed in the granular layer of the dentate gyrus, in the pyramidal neurons of CA3 region, and in the hippocampal