The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Nfatc1  -  nuclear factor of activated T cells,...

Mus musculus

Synonyms: 2210017P03Rik, AI449492, AV076380, NF-ATc, NF-ATc1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Nfatc1


High impact information on Nfatc1

  • This phenotype is associated with an elevated level of ras signaling in Nf1(-/-) endothelial cells and greater nuclear localization of the transcription factor Nfatc1 [6].
  • Since calcineurin is thought to control nuclear localization of NFATc proteins, we introduced a mutation into the calcineurin B gene that prevents phosphatase activation by Ca(2+) signals [7].
  • Among NFAT proteins, NFATc1 is crucial for the differentiation of bone-resorbing osteoclasts [8].
  • Thus, IGF-1 induces calcineurin-mediated signalling and activation of GATA-2, a marker of skeletal muscle hypertrophy, which cooperates with selected NF-ATc isoforms to activate gene expression programs [9].
  • We propose that growth-factor-induced skeletal-muscle hypertrophy and changes in myofibre phenotype are mediated by calcium mobilization and are critically regulated by the calcineurin/NF-ATc1 signalling pathway [10].

Biological context of Nfatc1

  • In fact, bone formation is inhibited in Nfatc1- and Nfatc2-deficient cells as well as in FK506-treated osteoblasts [8].
  • Characterization of Nfatc1 regulation identifies an enhancer required for gene expression that is specific to pro-valve endocardial cells in the developing heart [11].
  • Thus, autoregulation of Nfatc1 is required for maintaining high Nfatc1 expression in pro-valve endocardial cells, while suppression through the Hox site prevents its expression outside pro-valve endocardial cells during valve development [11].
  • Our data demonstrate the first autonomous cell-specific enhancer for pro-valve endocardial cells and delineate a unique transcriptional mechanism that regulates endocardial Nfatc1 expression within developing cardiac valves [11].
  • Interestingly, expression of Sox4 in the outflow tract and cushions of Foxp1 null embryos is significantly reduced, while remodeling of the cushions is disrupted, as demonstrated by reduced apoptosis and persistent Nfatc1 expression in the cushion mesenchyme [1].

Anatomical context of Nfatc1

  • Nfatc1 is an endocardial transcription factor required for development of cardiac valves [11].
  • This study suggests that pre-existing NFATc2 contributes to the subsequent induction of Nfatc1 during T cell activation [12].
  • Microarray analysis revealed that Nfatc1, another key regulator of osteoclastogenesis, was down-regulated in Fos(-/-) osteoclast precursors [13].
  • Of great surprise is the function of Cx45 in the endothelium, where it is essential for synchronized activation of the transcription factor Nfatc1 [14].
  • By using RAG-2-deficient blastocyst complementation, we now demonstrate that young, highly chimeric mice lacking NF-ATc have impaired repopulation of both thymus and peripheral lymphoid organs [15].

Associations of Nfatc1 with chemical compounds

  • However, we demonstrate that the constitutive nuclear ARE-associated factors react with Abs, raised to NF-ATp and NF-ATc, preferentially bind to the ARE but not to the NF-AT binding site and are cyclosporin A sensitive [16].
  • Pharmacologic inhibitors Gö6976 and rottlerin demonstrate that both conventional and novel protein kinase C (PKC) family members regulate endogenous mast cell NFAT activity, and NFAT2 TA [17].
  • A high cell density appeared to cause a change in the composition of the culture medium accompanying downregulation of NFAT2 expression, and we identified L-serine (LSer) as essential for the expression of NFAT2 induced by RANKL [18].
  • We therefore examined the role of NFATc1 in human beta(3) integrin expression in osteoclast differentiation [19].
  • Green fluorescence protein (GFP) or FLAG fusion proteins of either wild-type or constitutively active mutant NFATc [NFATc(S-->A)] were expressed in cultured adult mouse skeletal muscle fibers from flexor digitorum brevis (predominantly fast-twitch) [20].

Regulatory relationships of Nfatc1

  • In addition, the nuclear translocation of NFATc1 in the endocardial endothelial cells is inhibited in the Nkx2-5-/- embryos [21].
  • Interestingly, IL-4 potently inhibited RANKL-induced expression of NFATc1 at mRNA level [22].
  • Expression of NFAT2 increased the expression of IL-4 in both NKT cells and conventional T cells, and NFAT2 activated IL-10 in conventional T cells but not in NKT cells [23].
  • These adaptations occurred despite the fact that CnA* muscles displayed threefold higher calcineurin activity and enhanced dephosphorylation of the calcineurin targets NFATc1, MEF2A, and MEF2D [24].
  • Lowering extracellular pH dramatically increased accumulation of NFATc1 in nuclei of rat and rabbit osteoclasts to levels comparable with those induced by the proresorptive cytokine receptor activator of NF-kappaB ligand (RANKL) [25].

Other interactions of Nfatc1


Analytical, diagnostic and therapeutic context of Nfatc1


  1. Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. Wang, B., Weidenfeld, J., Lu, M.M., Maika, S., Kuziel, W.A., Morrisey, E.E., Tucker, P.W. Development (2004) [Pubmed]
  2. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Arron, J.R., Winslow, M.M., Polleri, A., Chang, C.P., Wu, H., Gao, X., Neilson, J.R., Chen, L., Heit, J.J., Kim, S.K., Yamasaki, N., Miyakawa, T., Francke, U., Graef, I.A., Crabtree, G.R. Nature (2006) [Pubmed]
  3. Calcineurin/NFAT signaling in osteoblasts regulates bone mass. Winslow, M.M., Pan, M., Starbuck, M., Gallo, E.M., Deng, L., Karsenty, G., Crabtree, G.R. Dev. Cell (2006) [Pubmed]
  4. Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. Asagiri, M., Sato, K., Usami, T., Ochi, S., Nishina, H., Yoshida, H., Morita, I., Wagner, E.F., Mak, T.W., Serfling, E., Takayanagi, H. J. Exp. Med. (2005) [Pubmed]
  5. The transcription factor NF-ATc is essential for cardiac valve formation. Ranger, A.M., Grusby, M.J., Hodge, M.R., Gravallese, E.M., de la Brousse, F.C., Hoey, T., Mickanin, C., Baldwin, H.S., Glimcher, L.H. Nature (1998) [Pubmed]
  6. Nf1 has an essential role in endothelial cells. Gitler, A.D., Zhu, Y., Ismat, F.A., Lu, M.M., Yamauchi, Y., Parada, L.F., Epstein, J.A. Nat. Genet. (2003) [Pubmed]
  7. Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature. Graef, I.A., Chen, F., Chen, L., Kuo, A., Crabtree, G.R. Cell (2001) [Pubmed]
  8. NFAT and Osterix cooperatively regulate bone formation. Koga, T., Matsui, Y., Asagiri, M., Kodama, T., de Crombrugghe, B., Nakashima, K., Takayanagi, H. Nat. Med. (2005) [Pubmed]
  9. IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1. Musarò, A., McCullagh, K.J., Naya, F.J., Olson, E.N., Rosenthal, N. Nature (1999) [Pubmed]
  10. Skeletal muscle hypertrophy is mediated by a Ca2+-dependent calcineurin signalling pathway. Semsarian, C., Wu, M.J., Ju, Y.K., Marciniec, T., Yeoh, T., Allen, D.G., Harvey, R.P., Graham, R.M. Nature (1999) [Pubmed]
  11. Characterization of Nfatc1 regulation identifies an enhancer required for gene expression that is specific to pro-valve endocardial cells in the developing heart. Zhou, B., Wu, B., Tompkins, K.L., Boyer, K.L., Grindley, J.C., Baldwin, H.S. Development (2005) [Pubmed]
  12. Regulation of the murine Nfatc1 gene by NFATc2. Zhou, B., Cron, R.Q., Wu, B., Genin, A., Wang, Z., Liu, S., Robson, P., Baldwin, H.S. J. Biol. Chem. (2002) [Pubmed]
  13. Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. Matsuo, K., Galson, D.L., Zhao, C., Peng, L., Laplace, C., Wang, K.Z., Bachler, M.A., Amano, H., Aburatani, H., Ishikawa, H., Wagner, E.F. J. Biol. Chem. (2004) [Pubmed]
  14. Regulation of the epithelial-mesenchymal transformation through gap junction channels in heart development. Nishii, K., Kumai, M., Shibata, Y. Trends Cardiovasc. Med. (2001) [Pubmed]
  15. Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc. Ranger, A.M., Hodge, M.R., Gravallese, E.M., Oukka, M., Davidson, L., Alt, F.W., de la Brousse, F.C., Hoey, T., Grusby, M., Glimcher, L.H. Immunity (1998) [Pubmed]
  16. Characterization of the constitutive and inducible components of a T cell IL-4 activation responsive element. Tara, D., Weiss, D.L., Brown, M.A. J. Immunol. (1995) [Pubmed]
  17. Nuclear factor of activated T cells 2 transactivation in mast cells: a novel isoform-specific transactivation domain confers unique FcepsilonRI responsiveness. Hock, M.B., Brown, M.A. J. Biol. Chem. (2003) [Pubmed]
  18. A novel role of L-serine (L-Ser) for the expression of nuclear factor of activated T cells (NFAT)2 in receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclastogenesis in vitro. Ogawa, T., Ishida-Kitagawa, N., Tanaka, A., Matsumoto, T., Hirouchi, T., Akimaru, M., Tanihara, M., Yogo, K., Takeya, T. J. Bone Miner. Metab. (2006) [Pubmed]
  19. NFATc1 regulation of the human beta(3) integrin promoter in osteoclast differentiation. Crotti, T.N., Flannery, M., Walsh, N.C., Fleming, J.D., Goldring, S.R., McHugh, K.P. Gene (2006) [Pubmed]
  20. Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers. Liu, Y., Cseresnyés, Z., Randall, W.R., Schneider, M.F. J. Cell Biol. (2001) [Pubmed]
  21. Dysregulation of connexins and inactivation of NFATc1 in the cardiovascular system of Nkx2-5 null mutants. Dupays, L., Jarry-Guichard, T., Mazurais, D., Calmels, T., Izumo, S., Gros, D., Théveniau-Ruissy, M. J. Mol. Cell. Cardiol. (2005) [Pubmed]
  22. Interleukin-4 inhibits RANKL-induced expression of NFATc1 and c-Fos: a possible mechanism for downregulation of osteoclastogenesis. Kamel Mohamed, S.G., Sugiyama, E., Shinoda, K., Hounoki, H., Taki, H., Maruyama, M., Miyahara, T., Kobayashi, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  23. Regulation of Th2 cytokine expression in NKT cells: unconventional use of Stat6, GATA-3, and NFAT2. Wang, Z.Y., Kusam, S., Munugalavadla, V., Kapur, R., Brutkiewicz, R.R., Dent, A.L. J. Immunol. (2006) [Pubmed]
  24. Matching of calcineurin activity to upstream effectors is critical for skeletal muscle fiber growth. Dunn, S.E., Chin, E.R., Michel, R.N. J. Cell Biol. (2000) [Pubmed]
  25. Convergent signaling by acidosis and receptor activator of NF-kappaB ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts. Komarova, S.V., Pereverzev, A., Shum, J.W., Sims, S.M., Dixon, S.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  26. Morphine negatively regulates interferon-gamma promoter activity in activated murine T cells through two distinct cyclic AMP-dependent pathways. Wang, J., Barke, R.A., Charboneau, R., Loh, H.H., Roy, S. J. Biol. Chem. (2003) [Pubmed]
  27. Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp. Li, X., Ho, S.N., Luna, J., Giacalone, J., Thomas, D.J., Timmerman, L.A., Crabtree, G.R., Francke, U. Cytogenet. Cell Genet. (1995) [Pubmed]
  28. RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation. Sundaram, K., Nishimura, R., Senn, J., Youssef, R.F., London, S.D., Reddy, S.V. Exp. Cell Res. (2007) [Pubmed]
  29. Molecular cloning and functional characterization of murine cDNA encoding transcription factor NFATc. Pan, S., Koyano-Nakagawa, N., Tsuruta, L., Amasaki, Y., Yokota, T., Mori, S., Arai, N., Arai, K. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
WikiGenes - Universities