Biology:NFATC2
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Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the NFATC2 gene.[1]
Function
This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[2]
Clinical significance
Translocation forming an in frame fusions product between EWSR1 gene and the NFATc2 gene has been described in bone tumor with a Ewing sarcoma-like clinical appearance. The translocation breakpoint led to the loss of the controlling elements of the NFATc2 protein and the fusion of the N terminal region of the EWSR1 gene conferred constant activation of the protein.[3]
Interactions
NFATC2 has been shown to interact with MEF2D,[4] EP300,[5] IRF4[6] and Protein kinase Mζ.[7] Prostaglandin F2alpha stimulates a NFCT2 pathway stimulating growth of skeletal muscle cells.[8]
References
- ↑ "NF-AT components define a family of transcription factors targeted in T-cell activation". Nature 369 (6480): 497–502. Jun 1994. doi:10.1038/369497a0. PMID 8202141. Bibcode: 1994Natur.369..497N.
- ↑ "Entrez Gene: NFATC2 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4773.
- ↑ "The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology". Clinical Cancer Research 15 (7): 2259–68. Apr 2009. doi:10.1158/1078-0432.CCR-08-2184. PMID 19318479.
- ↑ "Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis". The EMBO Journal 19 (16): 4323–31. Aug 2000. doi:10.1093/emboj/19.16.4323. PMID 10944115.
- ↑ "Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP)". The Journal of Experimental Medicine 187 (12): 2031–6. Jun 1998. doi:10.1084/jem.187.12.2031. PMID 9625762.
- ↑ "Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression". The Journal of Experimental Medicine 195 (8): 1003–12. Apr 2002. doi:10.1084/jem.20011128. PMID 11956291.
- ↑ "Protein kinase Czeta phosphorylates nuclear factor of activated T cells and regulates its transactivating activity". The Journal of Biological Chemistry 277 (30): 27073–80. Jul 2002. doi:10.1074/jbc.M106983200. PMID 12021260.
- ↑ Horsley V, Pavlath GK (2003). "Prostaglandin F2(alpha) stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway.". J Cell Biol 161 (1): 111–8. doi:10.1083/jcb.200208085. PMID 12695501.
Further reading
- "Transcription factors of the NFAT family: regulation and function". Annual Review of Immunology 15: 707–747. 1997. doi:10.1146/annurev.immunol.15.1.707. PMID 9143705.
- "Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT". Cell 96 (5): 611–614. Mar 1999. doi:10.1016/S0092-8674(00)80571-1. PMID 10089876.
- "NFAT: ubiquitous regulator of cell differentiation and adaptation". The Journal of Cell Biology 156 (5): 771–774. Mar 2002. doi:10.1083/jcb.200111073. PMID 11877454.
- "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 182 (3): 801–810. Sep 1995. doi:10.1084/jem.182.3.801. PMID 7650486.
- "[IMAGE: molecular integration of the analysis of the human genome and its expression]". Comptes Rendus de l'Académie des Sciences, Série III 318 (2): 263–72. Feb 1995. PMID 7757816.
- "Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp". Cytogenetics and Cell Genetics 68 (3–4): 185–191. 1995. doi:10.1159/000133910. PMID 7842733.
- "Cloning and Characterization of NF-ATc and NF-ATp: The Cytoplasmic Components of NF-AT". Mechanisms of Lymphocyte Activation and Immune Regulation V. Advances in Experimental Medicine and Biology. 365. 1994. pp. 167–73. doi:10.1007/978-1-4899-0987-9_17. ISBN 978-1-4899-0989-3.
- "Interaction of HIV gp120 and anti-CD4 antibodies with the CD4 molecule on human CD4+ T cells inhibits the binding activity of NF-AT, NF-kappa B and AP-1, three nuclear factors regulating interleukin-2 gene enhancer activity". European Journal of Immunology 24 (11): 2646–2652. Nov 1994. doi:10.1002/eji.1830241112. PMID 7957556.
- "Human immunodeficiency virus type-1 tat enhances interleukin-2 promoter activity through synergism with phorbol ester and calcium-mediated activation of the NF-AT cis-regulatory motif". Biochemical and Biophysical Research Communications 205 (1): 467–474. Nov 1994. doi:10.1006/bbrc.1994.2689. PMID 7999066.
- "The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun". Nature 365 (6444): 352–355. Sep 1993. doi:10.1038/365352a0. PMID 8397339. Bibcode: 1993Natur.365..352J.
- "Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes". Molecular and Cellular Biology 16 (7): 3955–66. Jul 1996. doi:10.1128/mcb.16.7.3955. PMID 8668213.
- "Cyclosporin A sensitivity of the HIV-1 long terminal repeat identifies distinct p56lck-dependent pathways activated by CD4 triggering". European Journal of Immunology 26 (9): 2181–2188. Sep 1996. doi:10.1002/eji.1830260933. PMID 8814265.
- "Suppression of the human immunodeficiency virus long terminal repeat by CD8+ T cells is dependent on the NFAT-1 element". AIDS Research and Human Retroviruses 12 (2): 143–148. Jan 1996. doi:10.1089/aid.1996.12.143. PMID 8834464.
- "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research 6 (9): 791–806. Sep 1996. doi:10.1101/gr.6.9.791. PMID 8889548.
- "NF-AT-Driven interleukin-4 transcription potentiated by NIP45". Science 274 (5294): 1903–1905. Dec 1996. doi:10.1126/science.274.5294.1903. PMID 8943202. Bibcode: 1996Sci...274.1903H.
- "Expression of NFAT-family proteins in normal human T cells". Molecular and Cellular Biology 17 (5): 2475–84. May 1997. doi:10.1128/mcb.17.5.2475. PMID 9111316.
- "Distinct NFAT family proteins are involved in the nuclear NFAT-DNA binding complexes from human thymocyte subsets". Journal of Immunology 160 (5): 2324–33. Mar 1998. doi:10.4049/jimmunol.160.5.2324. PMID 9498773.
- "Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA". Nature 392 (6671): 42–48. Mar 1998. doi:10.1038/32100. PMID 9510247. Bibcode: 1998Natur.392...42C.
External links
- NFATC2+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
![]() | Original source: https://en.wikipedia.org/wiki/NFATC2.
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