Gene Symbol: Nfatc3
Description: nuclear factor of activated T-cells 3
Alias: NFAT4, nuclear factor of activated T-cells, cytoplasmic 3, T cell transcription factor NFAT4, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3
Species: rat
Products:     Nfatc3

Top Publications

  1. de Frutos S, Spangler R, Alò D, Bosc L. NFATc3 mediates chronic hypoxia-induced pulmonary arterial remodeling with alpha-actin up-regulation. J Biol Chem. 2007;282:15081-9 pubmed
    ..b>NFATc3 (nuclear factor of activated T cells isoform c3), which is aCa(2+)-dependent transcription factor, has been ..
  2. Li G, Zhang X, Li R, Wang Y, Wang Y, Han K, et al. CHP2 activates the calcineurin/nuclear factor of activated T cells signaling pathway and enhances the oncogenic potential of HEK293 cells. J Biol Chem. 2008;283:32660-8 pubmed publisher
    ..In accord with this, CHP2-transfected cells showed increased nuclear presence of NFATc3 (nuclear factor of activated T cells) and enhanced NFAT activity...
  3. Phuong T, Yun Y, Kim S, Kang T. Positive feedback control between STIM1 and NFATc3 is required for C2C12 myoblast differentiation. Biochem Biophys Res Commun. 2013;430:722-8 pubmed publisher
    ..Transient increase of NFATc3 expression was observed in the initial phase of differentiation, and the increased activity of NFATc3 isoform was ..
  4. Fujii T, Onohara N, Maruyama Y, Tanabe S, Kobayashi H, Fukutomi M, et al. Galpha12/13-mediated production of reactive oxygen species is critical for angiotensin receptor-induced NFAT activation in cardiac fibroblasts. J Biol Chem. 2005;280:23041-7 pubmed
    ..Ang II-induced nuclear translocation of the green fluorescent protein (GFP)-tagged amino-terminal region of NFAT4 (GFP-NFAT4) was suppressed by p115-RGS or BAPTA but not by diphenyleneiodonium...
  5. Jayanthi S, Deng X, Ladenheim B, McCoy M, Cluster A, Cai N, et al. Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis. Proc Natl Acad Sci U S A. 2005;102:868-73 pubmed
    ..These observations indicate that METH causes some of its neurodegenerative effects, in part, via stimulation of the Fas-mediated cell death pathway consequent to FasL up-regulation mediated by activation of multiple TFs. ..
  6. Jones E, Sun D, Kobierski L, Symes A. NFAT4 is expressed in primary astrocytes and activated by glutamate. J Neurosci Res. 2003;72:191-7 pubmed
    ..We report here that NFAT4 is expressed in U373 astrocytoma cells and in primary cultures of astrocytes...
  7. Gómez Sintes R, Lucas J. NFAT/Fas signaling mediates the neuronal apoptosis and motor side effects of GSK-3 inhibition in a mouse model of lithium therapy. J Clin Invest. 2010;120:2432-45 pubmed publisher
    ..We found that GSK-3 inhibition increased translocation of nuclear factor of activated T cells c3/4 (NFATc3/4) transcription factors to the nucleus, leading to increased Fas ligand (FasL) levels and Fas activation...
  8. Lin Z, Murtaza I, Wang K, Jiao J, Gao J, Li P. miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy. Proc Natl Acad Sci U S A. 2009;106:12103-8 pubmed publisher
    ..miRNA, and its expression is regulated by the transcription factor, nuclear factor of activated T cells (NFATc3)...
  9. Manukyan I, Galatioto J, Mascareno E, Bhaduri S, Siddiqui M. Cross-talk between calcineurin/NFAT and Jak/STAT signalling induces cardioprotective alphaB-crystallin gene expression in response to hypertrophic stimuli. J Cell Mol Med. 2010;14:1707-16 pubmed publisher

More Information


  1. Luo X, Pan Z, Shan H, Xiao J, Sun X, Wang N, et al. MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation. J Clin Invest. 2013;123:1939-51 pubmed publisher
    ..Our results demonstrate that miR-26 controls the expression of KCNJ2 and suggest that this downregulation may promote AF...
  2. Dai Y, Xu J, Molkentin J. The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment. Mol Cell Biol. 2005;25:9936-48 pubmed
    ..Here we show that NFATc3, in addition to being calcium responsive, is regulated through an indirect recruitment of class II histone ..
  3. Wilkins B, Molkentin J. Calcium-calcineurin signaling in the regulation of cardiac hypertrophy. Biochem Biophys Res Commun. 2004;322:1178-91 pubmed
    ..Finally, we will discuss emerging theories as to the mechanisms whereby alterations in intracellular calcium handling might stimulate calcineurin within the context of a contractile cell continually experiencing calcium flux. ..
  4. Amberg G, Rossow C, Navedo M, Santana L. NFATc3 regulates Kv2.1 expression in arterial smooth muscle. J Biol Chem. 2004;279:47326-34 pubmed
    ..Consistent with our hypothesis, we found that calcineurin and NFATc3 are obligatory components of the signaling cascade mediating reduced IKv by Ang II...
  5. Bai S, Kerppola T. Opposing roles of FoxP1 and Nfat3 in transcriptional control of cardiomyocyte hypertrophy. Mol Cell Biol. 2011;31:3068-80 pubmed publisher
    ..FoxP1 counteracted hypertrophic cardiomyocyte growth, and connexin 43 mislocalization caused by cnNfat3 expression. These data suggest that the opposing transcriptional activities of FoxP1 and Nfat3 maintain cardiomyocyte homeostasis. ..
  6. Kegley K, Gephart J, Warren G, Pavlath G. Altered primary myogenesis in NFATC3(-/-) mice leads to decreased muscle size in the adult. Dev Biol. 2001;232:115-26 pubmed
    ..The purpose of this study was to determine the role of the NFATC3 isoform in skeletal muscle development...
  7. Kim M, Shutov L, Gnanasekaran A, Lin Z, Rysted J, ULRICH J, et al. Nerve growth factor (NGF) regulates activity of nuclear factor of activated T-cells (NFAT) in neurons via the phosphatidylinositol 3-kinase (PI3K)-Akt-glycogen synthase kinase 3β (GSK3β) pathway. J Biol Chem. 2014;289:31349-60 pubmed publisher
    ..Knockdown or knockout of NFATc3 eliminated this facilitatory effect...
  8. Hou X, Chen J, Luo Y, Liu F, Xu G, Gao Y. Silencing of STIM1 attenuates hypoxia-induced PASMCs proliferation via inhibition of the SOC/Ca2+/NFAT pathway. Respir Res. 2013;14:2 pubmed publisher
    ..The SOC-mediated Ca2+ influx was calculated by Ca2+ fluorescence imaging and the nuclear translocation of NFATc3 was determined by immunofluorescence and Western blot analysis of nuclear extracts...
  9. Nguyen T, Lindner R, Tedeschi A, Forsberg K, Green A, Wuttke A, et al. NFAT-3 is a transcriptional repressor of the growth-associated protein 43 during neuronal maturation. J Biol Chem. 2009;284:18816-23 pubmed publisher
    ..Taken together, our data reveal an unexpected role for NFAT-3 as a direct transcriptional repressor of GAP-43 expression and suggest a more general role for NFAT-3 in the control of the neuronal outgrowth program. ..
  10. ULRICH J, Kim M, Houlihan P, Shutov L, Mohapatra D, Strack S, et al. Distinct activation properties of the nuclear factor of activated T-cells (NFAT) isoforms NFATc3 and NFATc4 in neurons. J Biol Chem. 2012;287:37594-609 pubmed publisher
    ..Here, we compare the activation of NFATc3 and NFATc4 in hippocampal and dorsal root ganglion neurons following electrically evoked elevations of ..
  11. Kao S, Wu H, Xie J, Chang C, Ranish J, Graef I, et al. Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation. Science. 2009;323:651-4 pubmed publisher
    ..initiates an increase in cytoplasmic Ca2+, which activates calcineurin and the downstream transcription factors NFATc3 and c4...
  12. Yissachar N, Sharar Fischler T, Cohen A, Reich Zeliger S, Russ D, Shifrut E, et al. Dynamic response diversity of NFAT isoforms in individual living cells. Mol Cell. 2013;49:322-30 pubmed publisher, using imaging of individual living mammalian cells, that the closely related transcription factors NFAT1 and NFAT4 possess distinct nuclear localization dynamics in response to cell stimulation...
  13. Valdés J, Flores S, Fuentes E, Osorio Fuentealba C, Jaimovich E, Molina A. IGF-1 induces IP3 -dependent calcium signal involved in the regulation of myostatin gene expression mediated by NFAT during myoblast differentiation. J Cell Physiol. 2013;228:1452-63 pubmed publisher
    ..IP3 and induced by IGF-1 stimulates NFAT-dependent gene transcription and nuclear translocation of the GFP-labeled NFATc3 isoform...
  14. Yan H, Shin S, Ma X, Li Y, Dixon C. Differential effect of traumatic brain injury on the nuclear factor of activated T Cells C3 and C4 isoforms in the rat hippocampus. Brain Res. 2014;1548:63-72 pubmed publisher
    ..To determine if there is an alteration in NFAT after TBI, we examined NFATc3 and c4 levels at 6 h, 1 day, 1 week, 2 weeks and 4 weeks post injury...
  15. Filosa J, Nelson M, Gonzalez Bosc L. Activity-dependent NFATc3 nuclear accumulation in pericytes from cortical parenchymal microvessels. Am J Physiol Cell Physiol. 2007;293:C1797-805 pubmed
    The calcium-dependent transcription factor NFATc3, which is a member of the nuclear factor of activated T cells (NFAT) family of transcription factors, is critical for embryonic vascular development and differentiation...
  16. Lejard V, Brideau G, Blais F, Salingcarnboriboon R, Wagner G, Roehrl M, et al. Scleraxis and NFATc regulate the expression of the pro-alpha1(I) collagen gene in tendon fibroblasts. J Biol Chem. 2007;282:17665-75 pubmed
    ..Taken together, these results suggest that SCX and NFATc4 cooperate to activate the COL1a1 gene specifically in tendon fibroblasts. ..
  17. Zhao L, Sullivan M, Chase M, Gonzales A, Earley S. Calcineurin/nuclear factor of activated T cells-coupled vanilliod transient receptor potential channel 4 ca2+ sparklets stimulate airway smooth muscle cell proliferation. Am J Respir Cell Mol Biol. 2014;50:1064-75 pubmed publisher
    ..proliferation in response to TRPV4 activity is associated with calcineurin-dependent nuclear translocation of the NFATc3 isoform tagged with green florescent protein...
  18. Goruppi S, Kyriakis J. The pro-hypertrophic basic helix-loop-helix protein p8 is degraded by the ubiquitin/proteasome system in a protein kinase B/Akt- and glycogen synthase kinase-3-dependent manner, whereas endothelin induction of p8 mRNA and renal mesangial cell hypertr. J Biol Chem. 2004;279:20950-8 pubmed
    ..experiments indicated that ET-1-stimulated mesangial cell hypertrophy and p8 mRNA induction require the NFAT4 transcription factor...
  19. Ho S, Thomas D, Timmerman L, Li X, Francke U, Crabtree G. NFATc3, a lymphoid-specific NFATc family member that is calcium-regulated and exhibits distinct DNA binding specificity. J Biol Chem. 1995;270:19898-907 pubmed
    ..roles of antigen receptor signaling throughout T cell development, we have identified a new NFATc family member, NFATc3, that is expressed at highest levels in the thymus...
  20. Liu C, Cheng Y, Lee K, Hsu H, Chu C, Tsai F, et al. Lipopolysaccharide induces cellular hypertrophy through calcineurin/NFAT-3 signaling pathway in H9c2 myocardiac cells. Mol Cell Biochem. 2008;313:167-78 pubmed publisher
    ..Our findings further provide a link between the LPS-induced inflammatory response and the calcineurin/NFAT-3 signaling pathway that mediates the development of cardiac hypertrophy. ..
  21. Li H, Gao S, Ye J, Feng X, Cai Y, Liu Z, et al. COX-2 is involved in ET-1-induced hypertrophy of neonatal rat cardiomyocytes: role of NFATc3. Mol Cell Endocrinol. 2014;382:998-1006 pubmed publisher
    ..Furthermore, cyclosporin A (CsA) and knockdown of nuclear factor of activated T-cells c3 (NFATc3) inhibited the expression of COX-2 induced by ET-1, and NFATc3 could also bound to the -GGAAA- sequence in the ..
  22. Benedito A, Lehtinen M, Massol R, Lopes U, Kirchhausen T, Rao A, et al. The transcription factor NFAT3 mediates neuronal survival. J Biol Chem. 2005;280:2818-25 pubmed
    ..Taken together, these results reveal an essential function for NFAT3-mediated transcription in neuronal survival that may play important roles in the developing and mature brain. ..
  23. Wang K, Long B, Zhou J, Li P. miR-9 and NFATc3 regulate myocardin in cardiac hypertrophy. J Biol Chem. 2010;285:11903-12 pubmed publisher
    ..Our present study reveals that nuclear factor of activated T cells c3 (NFATc3) and myocardin constitute a hypertrophic pathway that can be targeted by miR-9...
  24. Ran Y, Wu H, Wei L, Yu X, Chen J, Li S, et al. NFATc3 pathway participates in the process that 15-LO/15-HETE protects pulmonary artery smooth muscle cells against apoptosis during hypoxia. J Recept Signal Transduct Res. 2014;34:270-82 pubmed publisher
    Hypoxia activates nuclear factor of activated T cells isoforms c3 (NFATc3), a Ca(2+)-dependent transcription factor in murine pulmonary arteries (PAs), and NFATc3 has been proved to be implicated in hypoxia-induced pulmonary arterial ..
  25. Bushdid P, Osinska H, Waclaw R, Molkentin J, Yutzey K. NFATc3 and NFATc4 are required for cardiac development and mitochondrial function. Circ Res. 2003;92:1305-13 pubmed
    ..In this report, the function of NFATc3 and NFATc4 in embryonic heart development was examined in mice with targeted disruption of both nfatc3 and nfatc4 ..
  26. Wilkins B, De Windt L, Bueno O, Braz J, Glascock B, Kimball T, et al. Targeted disruption of NFATc3, but not NFATc4, reveals an intrinsic defect in calcineurin-mediated cardiac hypertrophic growth. Mol Cell Biol. 2002;22:7603-13 pubmed
    ..Accordingly, mice with targeted disruptions in NFATc3 and NFATc4 genes were characterized...
  27. Bueno O, Brandt E, Rothenberg M, Molkentin J. Defective T cell development and function in calcineurin A beta -deficient mice. Proc Natl Acad Sci U S A. 2002;99:9398-403 pubmed
    ..suggested by the observation that CnA beta(-/-) T cells are defective in stimulation-induced NFATc1, NFATc2, and NFATc3 activation...
  28. Rengarajan J, Mittelstadt P, Mages H, Gerth A, Kroczek R, Ashwell J, et al. Sequential involvement of NFAT and Egr transcription factors in FasL regulation. Immunity. 2000;12:293-300 pubmed
    ..critical function of NFAT proteins in maintaining lymphoid homeostasis was revealed in mice lacking both NFATp and NFAT4 (DKO)...
  29. Molkentin J, Lu J, Antos C, Markham B, Richardson J, Robbins J, et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998;93:215-28 pubmed
    ..Pharmacologic inhibition of calcineurin activity blocks hypertrophy in vivo and in vitro. These results define a novel hypertrophic signaling pathway and suggest pharmacologic approaches to prevent cardiac hypertrophy and heart failure. ..
  30. Dittmer P, Wild A, Dell Acqua M, Sather W. STIM1 Ca2+ Sensor Control of L-type Ca2+-Channel-Dependent Dendritic Spine Structural Plasticity and Nuclear Signaling. Cell Rep. 2017;19:321-334 pubmed publisher the neurotransmitter glutamate, resulting in regulation of spine ER structure and nuclear signaling by the NFATc3 transcription factor...
  31. Lee H, Bae O, Baek K, Kwon A, Hwang H, Qadir A, et al. High extracellular calcium-induced NFATc3 regulates the expression of receptor activator of NF-?B ligand in osteoblasts. Bone. 2011;49:242-9 pubmed publisher
    ..Among the family of NFAT transcription factors, expression of NFATc1 and NFATc3, but not NFATc2, NFATc4 or NFAT5, was observed in MC4 cells...
  32. Armand A, Bourajjaj M, Martínez Martínez S, el Azzouzi H, da Costa Martins P, Hatzis P, et al. Cooperative synergy between NFAT and MyoD regulates myogenin expression and myogenesis. J Biol Chem. 2008;283:29004-10 pubmed publisher
    ..assays, we identified two conserved NFAT binding sites in the myogenin promoter that were occupied by NFATc3 upon skeletal muscle differentiation...
  33. Alfieri C, Evans Anderson H, Yutzey K. Developmental regulation of the mouse IGF-I exon 1 promoter region by calcineurin activation of NFAT in skeletal muscle. Am J Physiol Cell Physiol. 2007;292:C1887-94 pubmed developing skeletal muscle, and its embryonic expression is significantly reduced in embryos lacking both NFATc3 and NFATc4...
  34. Dave V, Childs T, Xu Y, Ikegami M, Besnard V, Maeda Y, et al. Calcineurin/Nfat signaling is required for perinatal lung maturation and function. J Clin Invest. 2006;116:2597-609 pubmed
    ..Nuclear factor of activated T cells (Nfat) calcineurin-dependent 3 (Nfatc3), a transcription factor modulated by calcineurin, was identified as a direct activator of Sftpa, Sftpb, Sftpc, ..
  35. Dave V, Childs T, Whitsett J. Nuclear factor of activated T cells regulates transcription of the surfactant protein D gene (Sftpd) via direct interaction with thyroid transcription factor-1 in lung epithelial cells. J Biol Chem. 2004;279:34578-88 pubmed
    ..Calcineurin and NFATc3 proteins were detected in the embryonic and adult mouse lung epithelium, and the mRNA expression profiles of the ..
  36. Pouillon V, Hascakova Bartova R, Pajak B, Adam E, Bex F, Dewaste V, et al. Inositol 1,3,4,5-tetrakisphosphate is essential for T lymphocyte development. Nat Immunol. 2003;4:1136-43 pubmed
    ..These data indicate that Itpkb and Ins(1,3,4,5)P(4) define an essential signaling pathway for T cell precursor responsiveness and development. ..
  37. Oukka M, Ho I, de la Brousse F, Hoey T, Grusby M, Glimcher L. The transcription factor NFAT4 is involved in the generation and survival of T cells. Immunity. 1998;9:295-304 pubmed
    ..Here we report that NFAT4, in contrast to NFATp and NFATc, is preferentially expressed in DP thymocytes...
  38. Liu J, Koyano Nakagawa N, Amasaki Y, Saito Ohara F, Ikeuchi T, Imai S, et al. Calcineurin-dependent nuclear translocation of a murine transcription factor NFATx: molecular cloning and functional characterization. Mol Biol Cell. 1997;8:157-70 pubmed
    ..These results provide the first evidence for the requirement of calcineurin in the control of mNFATx imported from the cytoplasm to the nucleus and implies that mNFATx may possibly be a substrate of calcineurin in vivo. ..