NFATC2

Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
	; PDB rendering based on 1a02.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1A02, 1OWR, 1P7H, 1PZU, 1S9K, 2AS5, 2O93, 3QRF
Identifiers
Symbols	NFATC2; NFAT1; NFATP
External IDs	OMIM: 600490 MGI: 102463 HomoloGene: 7861 ChEMBL: 4120 GeneCards: NFATC2 Gene
Gene Ontology
Molecular function	• DNA binding; • sequence-specific DNA binding transcription factor activity; • protein binding; • sequence-specific DNA binding; • transcription regulatory region DNA binding;
Cellular component	• nucleus; • nucleolus; • cytoplasm; • cytosol; • plasma membrane; • actin cytoskeleton; • ribonucleoprotein complex;
Biological process	• cytokine production; • transcription, DNA-dependent; • regulation of transcription, DNA-dependent; • response to DNA damage stimulus; • cell migration; • positive regulation of B cell proliferation; • response to drug; • positive regulation of transcription, DNA-dependent; • positive regulation of transcription from RNA polymerase II promoter; • B cell receptor signaling pathway;
	Sources: Amigo / QuickGO
Orthologs
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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]

[edit] 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]

[edit] Clinical significance

NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation. Indeed NFAT1 (NFATC2) is pro-invasive and pro-migratory in breast carcinoma.^[3]^[4]

To increase cell motility NFAT1 up-regulates the gene of the Lipocalin 2 expression and modulate the TWEAKR/TWEAK axis.^[5]

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. ^[6]

[edit] Interactions

NFATC2 has been shown to interact with MEF2D,^[7] EP300,^[8] IRF4^[9] and Protein kinase Mζ.^[10]

[edit] References

^ Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP, Admon A, Crabtree GR (July 1994). "NF-AT components define a family of transcription factors targeted in T-cell activation". Nature 369 (6480): 497–502. doi:10.1038/369497a0. PMID 8202141.
^ "Entrez Gene: NFATC2 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4773.
^ Jauliac S, López-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A (July 2002). "The role of NFAT transcription factors in integrin-mediated carcinoma invasion". Nat. Cell Biol. 4 (7): 540–4. doi:10.1038/ncb816. PMID 12080349.
^ Yoeli-Lerner M, Yiu GK, Rabinovitz I, Erhardt P, Jauliac S, Toker A (November 2005). "Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT". Mol. Cell 20 (4): 539–50. doi:10.1016/j.molcel.2005.10.033. PMID 16307918.
^ Gaudineau B, Fougère M, Guaddachi F, Lemoine F, de la Grange P, Jauliac S (July 2012). "Lipocalin 2 (LCN2), the TNF-like receptor TWEAKR and its ligand TWEAK act downstream of NFAT1 to regulate breast cancer cell invasion". J Cell Sci. doi:10.1242/jcs.099879. PMID 22767506.
^ Szuhai K, Ijszenga M, de Jong D, Karseladze A, Tanke HJ, Hogendoorn PCW (April 2009). "The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology". Clin Cancer Res 15 (7): 2259–68. doi:10.1158/1078-0432.CCR-08-2184. PMID 19318479.
^ Youn HD, Chatila TA, Liu JO (August 2000). "Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis". EMBO J. 19 (16): 4323–31. doi:10.1093/emboj/19.16.4323. PMC 302027. PMID 10944115.
^ García-Rodríguez C, Rao A (June 1998). "Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP)". J. Exp. Med. 187 (12): 2031–6. doi:10.1084/jem.187.12.2031. PMC 2212364. PMID 9625762.
^ Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH (April 2002). "Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression". J. Exp. Med. 195 (8): 1003–12. doi:10.1084/jem.20011128. PMC 2193700. PMID 11956291.
^ San-Antonio B, Iñiguez MA, Fresno M (July 2002). "Protein kinase Czeta phosphorylates nuclear factor of activated T cells and regulates its transactivating activity". J. Biol. Chem. 277 (30): 27073–80. doi:10.1074/jbc.M106983200. PMID 12021260.

[edit] Further reading

Rao A, Luo C, Hogan PG (1997). "Transcription factors of the NFAT family: regulation and function". Annu. Rev. Immunol. 15: 707–747. doi:10.1146/annurev.immunol.15.1.707. PMID 9143705.
Crabtree GR (1999). "Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT". Cell 96 (5): 611–614. doi:10.1016/S0092-8674(00)80571-1. PMID 10089876.
Horsley V, Pavlath GK (2002). "NFAT: ubiquitous regulator of cell differentiation and adaptation". J. Cell Biol. 156 (5): 771–774. doi:10.1083/jcb.200111073. PMC 2173310. PMID 11877454.
Aramburu J, Azzoni L, Rao A, Perussia B (1995). "Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding". J. Exp. Med. 182 (3): 801–810. doi:10.1084/jem.182.3.801. PMC 2192167. PMID 7650486.
Auffray C, Behar G, Bois F, Bouchier C, Da Silva C, Devignes MD, Duprat S, Houlgatte R, Jumeau MN, Lamy B, et al. (1995). "[IMAGE: molecular integration of the analysis of the human genome and its expression]". C. R. Acad. Sci. III, Sci. Vie 318 (2): 263–72. PMID 7757816.
Li X, Ho SN, Luna J, Giacalone J, Thomas DJ, Timmerman LA, Crabtree GR, Francke U (1995). "Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp". Cytogenet. Cell Genet. 68 (3–4): 185–191. doi:10.1159/000133910. PMID 7842733.
Ho S, Timmerman L, Northrop J, Crabtree GR (1995). "Cloning and characterization of NF-ATc and NF-ATp: the cytoplasmic components of NF-AT". Adv. Exp. Med. Biol. 365: 167–73. PMID 7887301.
Jabado N, Le Deist F, Fisher A, Hivroz C (1994). "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". Eur. J. Immunol. 24 (11): 2646–2652. doi:10.1002/eji.1830241112. PMID 7957556.
Vacca A, Farina M, Maroder M, Alesse E, Screpanti I, Frati L, Gulino A (1995). "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". Biochem. Biophys. Res. Commun. 205 (1): 467–474. doi:10.1006/bbrc.1994.2689. PMID 7999066.
Jain J, McCaffrey PG, Miner Z, Kerppola TK, Lambert JN, Verdine GL, Curran T, Rao A (1993). "The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun". Nature 365 (6444): 352–355. doi:10.1038/365352a0. PMID 8397339.
Luo C, Burgeon E, Carew JA, McCaffrey PG, Badalian TM, Lane WS, Hogan PG, Rao A (1996). "Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes". Mol. Cell. Biol. 16 (7): 3955–66. PMC 231392. PMID 8668213.
Di Somma MM, Majolini MB, Burastero SE, Telford JL, Baldari CT (1996). "Cyclosporin A sensitivity of the HIV-1 long terminal repeat identifies distinct p56lck-dependent pathways activated by CD4 triggering". Eur. J. Immunol. 26 (9): 2181–2188. doi:10.1002/eji.1830260933. PMID 8814265.
Copeland KF, McKay PJ, Rosenthal KL (1996). "Suppression of the human immunodeficiency virus long terminal repeat by CD8+ T cells is dependent on the NFAT-1 element". AIDS Res. Hum. Retroviruses 12 (2): 143–148. doi:10.1089/aid.1996.12.143. PMID 8834464.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Hodge MR, Chun HJ, Rengarajan J, Alt A, Lieberson R, Glimcher LH (1997). "NF-AT-Driven interleukin-4 transcription potentiated by NIP45". Science 274 (5294): 1903–1905. doi:10.1126/science.274.5294.1903. PMID 8943202.
Lyakh L, Ghosh P, Rice NR (1997). "Expression of NFAT-family proteins in normal human T cells". Mol. Cell. Biol. 17 (5): 2475–84. PMC 232096. PMID 9111316.
Amasaki Y, Masuda ES, Imamura R, Arai K, Arai N (1998). "Distinct NFAT family proteins are involved in the nuclear NFAT-DNA binding complexes from human thymocyte subsets". J. Immunol. 160 (5): 2324–33. PMID 9498773.
Chen L, Glover JN, Hogan PG, Rao A, Harrison SC (1998). "Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA". Nature 392 (6671): 42–48. doi:10.1038/32100. PMID 9510247.

[edit] External links

NFATC2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
[3]

This article on a gene on chromosome 20 is a stub. You can help Wikipedia by expanding it.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

[pmid8202141-1] Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP, Admon A, Crabtree GR (July 1994). "NF-AT components define a family of transcription factors targeted in T-cell activation". Nature 369 (6480): 497–502. doi:10.1038/369497a0. PMID 8202141.

[2] "Entrez Gene: NFATC2 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4773.

[pmid12080349-3] Jauliac S, López-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A (July 2002). "The role of NFAT transcription factors in integrin-mediated carcinoma invasion". Nat. Cell Biol. 4 (7): 540–4. doi:10.1038/ncb816. PMID 12080349.

[pmid16307918-4] Yoeli-Lerner M, Yiu GK, Rabinovitz I, Erhardt P, Jauliac S, Toker A (November 2005). "Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT". Mol. Cell 20 (4): 539–50. doi:10.1016/j.molcel.2005.10.033. PMID 16307918.

[pmid22767506-5] Gaudineau B, Fougère M, Guaddachi F, Lemoine F, de la Grange P, Jauliac S (July 2012). "Lipocalin 2 (LCN2), the TNF-like receptor TWEAKR and its ligand TWEAK act downstream of NFAT1 to regulate breast cancer cell invasion". J Cell Sci. doi:10.1242/jcs.099879. PMID 22767506.

[pmid19318479-6] Szuhai K, Ijszenga M, de Jong D, Karseladze A, Tanke HJ, Hogendoorn PCW (April 2009). "The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology". Clin Cancer Res 15 (7): 2259–68. doi:10.1158/1078-0432.CCR-08-2184. PMID 19318479.

[pmid10944115-7] Youn HD, Chatila TA, Liu JO (August 2000). "Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis". EMBO J. 19 (16): 4323–31. doi:10.1093/emboj/19.16.4323. PMC 302027. PMID 10944115.

[pmid9625762-8] García-Rodríguez C, Rao A (June 1998). "Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP)". J. Exp. Med. 187 (12): 2031–6. doi:10.1084/jem.187.12.2031. PMC 2212364. PMID 9625762.

[pmid11956291-9] Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH (April 2002). "Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression". J. Exp. Med. 195 (8): 1003–12. doi:10.1084/jem.20011128. PMC 2193700. PMID 11956291.

[pmid12021260-10] San-Antonio B, Iñiguez MA, Fresno M (July 2002). "Protein kinase Czeta phosphorylates nuclear factor of activated T cells and regulates its transactivating activity". J. Biol. Chem. 277 (30): 27073–80. doi:10.1074/jbc.M106983200. PMID 12021260.

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NFATC2

Contents

[edit] Function

[edit] Clinical significance

[edit] Interactions

[edit] References

[edit] Further reading

[edit] External links

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