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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Nuclear factor of activated T-cells, cytoplasmic 2''' is a [[protein]] that in humans is encoded by the ''NFATC2'' [[gene]].<ref name="pmid8202141">{{cite journal | vauthors = Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP, Admon A, Crabtree GR | title = NF-AT components define a family of transcription factors targeted in T-cell activation | journal = Nature | volume = 369 | issue = 6480 | pages = 497–502 | date = Jun 1994 | pmid = 8202141 | pmc = | doi = 10.1038/369497a0 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_NFATC2_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1a02.
| PDB = {{PDB2|1a02}}, {{PDB2|1owr}}, {{PDB2|1p7h}}, {{PDB2|1pzu}}, {{PDB2|1s9k}}, {{PDB2|2as5}}
| Name = Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
| HGNCid = 7776
| Symbol = NFATC2
| AltSymbols =; KIAA0611; NFAT1; NFATP
| OMIM = 600490
| ECnumber = 
| Homologene = 7861
| MGIid = 102463
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0016563 |text = transcription activator activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0001816 |text = cytokine production}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0045941 |text = positive regulation of transcription}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 4773
    | Hs_Ensembl = ENSG00000101096
    | Hs_RefseqProtein = NP_036472
    | Hs_RefseqmRNA = NM_012340
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 20
    | Hs_GenLoc_start = 49441083
    | Hs_GenLoc_end = 49592665
    | Hs_Uniprot = Q13469
    | Mm_EntrezGene = 18019
    | Mm_Ensembl = ENSMUSG00000027544
    | Mm_RefseqmRNA = NM_001037177
    | Mm_RefseqProtein = NP_001032254
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 2
    | Mm_GenLoc_start = 168167615
    | Mm_GenLoc_end = 168292860
    | Mm_Uniprot = Q6P3F6
  }}
}}
'''Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2''', also known as '''NFATC2''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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.<ref>{{cite web | title = Entrez Gene: NFATC2 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4773| accessdate = }}</ref>
{{PBB_Summary
| section_title =
| summary_text = 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.<ref>{{cite web | title = Entrez Gene: NFATC2 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4773| accessdate = }}</ref>
}}


==See also==
== Clinical significance ==
* [[NFAT]]


==References==
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.<ref name="pmid12080349">{{cite journal | vauthors = Jauliac S, López-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A | title = The role of NFAT transcription factors in integrin-mediated carcinoma invasion | journal = Nature Cell Biology | volume = 4 | issue = 7 | pages = 540–4 | date = Jul 2002 | pmid = 12080349 | doi = 10.1038/ncb816 }}</ref><ref name="pmid16307918">{{cite journal | vauthors = Yoeli-Lerner M, Yiu GK, Rabinovitz I, Erhardt P, Jauliac S, Toker A | title = Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT | journal = Molecular Cell | volume = 20 | issue = 4 | pages = 539–50 | date = Nov 2005 | pmid = 16307918 | doi = 10.1016/j.molcel.2005.10.033 }}</ref>
{{reflist|2}}


==Further reading==
To increase cell motility NFAT1 up-regulates the gene of the [[LCN2|Lipocalin 2]] expression and modulate the TWEAKR/TWEAK axis.<ref name="pmid22767506">{{cite journal | vauthors = Gaudineau B, Fougère M, Guaddachi F, Lemoine F, de la Grange P, Jauliac S | title = Lipocalin 2, the TNF-like receptor TWEAKR and its ligand TWEAK act downstream of NFAT1 to regulate breast cancer cell invasion | journal = Journal of Cell Science | volume = 125 | issue = Pt 19 | pages = 4475–86 | date = Oct 2012 | pmid = 22767506 | doi = 10.1242/jcs.099879 }}</ref>
 
Translocation forming an in frame fusions product between [[Ewing sarcoma breakpoint region 1|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.<ref name="pmid19318479">{{cite journal | vauthors = Szuhai K, Ijszenga M, de Jong D, Karseladze A, Tanke HJ, Hogendoorn PC | title = The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology | journal = Clinical Cancer Research | volume = 15 | issue = 7 | pages = 2259–68 | date = Apr 2009 | pmid = 19318479 | doi = 10.1158/1078-0432.CCR-08-2184 }}</ref>
 
== Interactions ==
 
NFATC2 has been shown to [[Protein-protein interaction|interact]] with [[MEF2D]],<ref name="pmid10944115">{{cite journal | vauthors = Youn HD, Chatila TA, Liu JO | title = Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis | journal = The EMBO Journal | volume = 19 | issue = 16 | pages = 4323–31 | date = Aug 2000 | pmid = 10944115 | pmc = 302027 | doi = 10.1093/emboj/19.16.4323 }}</ref> [[EP300]],<ref name="pmid9625762">{{cite journal | vauthors = García-Rodríguez C, Rao A | title = Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP) | journal = The Journal of Experimental Medicine | volume = 187 | issue = 12 | pages = 2031–6 | date = Jun 1998 | pmid = 9625762 | pmc = 2212364 | doi = 10.1084/jem.187.12.2031 }}</ref> [[IRF4]]<ref name="pmid11956291">{{cite journal | vauthors = Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH | title = Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression | journal = The Journal of Experimental Medicine | volume = 195 | issue = 8 | pages = 1003–12 | date = Apr 2002 | pmid = 11956291 | pmc = 2193700 | doi = 10.1084/jem.20011128 }}</ref> and [[Protein kinase Mζ]].<ref name="pmid12021260">{{cite journal | vauthors = San-Antonio B, Iñiguez MA, Fresno M | title = Protein kinase Czeta phosphorylates nuclear factor of activated T cells and regulates its transactivating activity | journal = The Journal of Biological Chemistry | volume = 277 | issue = 30 | pages = 27073–80 | date = Jul 2002 | pmid = 12021260 | doi = 10.1074/jbc.M106983200 }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Rao A, Luo C, Hogan PG | title = Transcription factors of the NFAT family: regulation and function | journal = Annual Review of Immunology | volume = 15 | issue =  | pages = 707–747 | year = 1997 | pmid = 9143705 | doi = 10.1146/annurev.immunol.15.1.707 }}
| citations =
* {{cite journal | vauthors = Crabtree GR | title = Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT | journal = Cell | volume = 96 | issue = 5 | pages = 611–614 | date = Mar 1999 | pmid = 10089876 | doi = 10.1016/S0092-8674(00)80571-1 }}
*{{cite journal | author=Rao A, Luo C, Hogan PG |title=Transcription factors of the NFAT family: regulation and function. |journal=Annu. Rev. Immunol. |volume=15 |issue=  |pages= 707-47 |year= 1997 |pmid= 9143705 |doi= 10.1146/annurev.immunol.15.1.707 }}
* {{cite journal | vauthors = Horsley V, Pavlath GK | title = NFAT: ubiquitous regulator of cell differentiation and adaptation | journal = The Journal of Cell Biology | volume = 156 | issue = 5 | pages = 771–774 | date = Mar 2002 | pmid = 11877454 | pmc = 2173310 | doi = 10.1083/jcb.200111073 }}
*{{cite journal | author=Crabtree GR |title=Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT. |journal=Cell |volume=96 |issue= 5 |pages= 611-4 |year= 1999 |pmid= 10089876 |doi= }}
* {{cite journal | vauthors = Aramburu J, Azzoni L, Rao A, Perussia B | title = Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding | journal = The Journal of Experimental Medicine | volume = 182 | issue = 3 | pages = 801–810 | date = Sep 1995 | pmid = 7650486 | pmc = 2192167 | doi = 10.1084/jem.182.3.801 }}
*{{cite journal | author=Horsley V, Pavlath GK |title=NFAT: ubiquitous regulator of cell differentiation and adaptation. |journal=J. Cell Biol. |volume=156 |issue= 5 |pages= 771-4 |year= 2002 |pmid= 11877454 |doi= 10.1083/jcb.200111073 }}
* {{cite journal | vauthors = Auffray C, Behar G, Bois F, Bouchier C, Da Silva C, Devignes MD, Duprat S, Houlgatte R, Jumeau MN, Lamy B | title = [IMAGE: molecular integration of the analysis of the human genome and its expression] | journal = Comptes Rendus De L'Académie Des Sciences. Série III, Sciences De La Vie | volume = 318 | issue = 2 | pages = 263–72 | date = Feb 1995 | pmid = 7757816 | doi =  }}
*{{cite journal | author=Aramburu J, Azzoni L, Rao A, Perussia B |title=Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding. |journal=J. Exp. Med. |volume=182 |issue= 3 |pages= 801-10 |year= 1995 |pmid= 7650486 |doi= }}
* {{cite journal | vauthors = Li X, Ho SN, Luna J, Giacalone J, Thomas DJ, Timmerman LA, Crabtree GR, Francke U | title = Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp | journal = Cytogenetics and Cell Genetics | volume = 68 | issue = 3-4 | pages = 185–191 | year = 1995 | pmid = 7842733 | doi = 10.1159/000133910 }}
*{{cite journal | author=Auffray C, Behar G, Bois F, ''et al.'' |title=[IMAGE: molecular integration of the analysis of the human genome and its expression] |journal=C. R. Acad. Sci. III, Sci. Vie |volume=318 |issue= 2 |pages= 263-72 |year= 1995 |pmid= 7757816 |doi=  }}
* {{cite journal | vauthors = Ho S, Timmerman L, Northrop J, Crabtree GR | title = Cloning and characterization of NF-ATc and NF-ATp: the cytoplasmic components of NF-AT | journal = Advances in Experimental Medicine and Biology | volume = 365 | issue =  | pages = 167–73 | year = 1995 | pmid = 7887301 | doi = 10.1007/978-1-4899-0987-9_17 }}
*{{cite journal | author=Li X, Ho SN, Luna J, ''et al.'' |title=Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp. |journal=Cytogenet. Cell Genet. |volume=68 |issue= 3-4 |pages= 185-91 |year= 1995 |pmid= 7842733 |doi= }}
* {{cite journal | vauthors = Jabado N, Le Deist F, Fisher A, Hivroz C | title = 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 | journal = European Journal of Immunology | volume = 24 | issue = 11 | pages = 2646–2652 | date = Nov 1994 | pmid = 7957556 | doi = 10.1002/eji.1830241112 }}
*{{cite journal | author=Ho S, Timmerman L, Northrop J, Crabtree GR |title=Cloning and characterization of NF-ATc and NF-ATp: the cytoplasmic components of NF-AT. |journal=Adv. Exp. Med. Biol. |volume=365 |issue=  |pages= 167-73 |year= 1995 |pmid= 7887301 |doi= }}
* {{cite journal | vauthors = Vacca A, Farina M, Maroder M, Alesse E, Screpanti I, Frati L, Gulino A | title = 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 | journal = Biochemical and Biophysical Research Communications | volume = 205 | issue = 1 | pages = 467–474 | date = Nov 1994 | pmid = 7999066 | doi = 10.1006/bbrc.1994.2689 }}
*{{cite journal | author=Jabado N, Le Deist F, Fisher A, Hivroz C |title=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. |journal=Eur. J. Immunol. |volume=24 |issue= 11 |pages= 2646-52 |year= 1994 |pmid= 7957556 |doi= }}
* {{cite journal | vauthors = Jain J, McCaffrey PG, Miner Z, Kerppola TK, Lambert JN, Verdine GL, Curran T, Rao A | title = The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun | journal = Nature | volume = 365 | issue = 6444 | pages = 352–355 | date = Sep 1993 | pmid = 8397339 | doi = 10.1038/365352a0 }}
*{{cite journal | author=Vacca A, Farina M, Maroder M, ''et al.'' |title=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. |journal=Biochem. Biophys. Res. Commun. |volume=205 |issue= 1 |pages= 467-74 |year= 1995 |pmid= 7999066 |doi= 10.1006/bbrc.1994.2689 }}
* {{cite journal | vauthors = Luo C, Burgeon E, Carew JA, McCaffrey PG, Badalian TM, Lane WS, Hogan PG, Rao A | title = Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes | journal = Molecular and Cellular Biology | volume = 16 | issue = 7 | pages = 3955–66 | date = Jul 1996 | pmid = 8668213 | pmc = 231392 | doi = }}
*{{cite journal | author=Northrop JP, Ho SN, Chen L, ''et al.'' |title=NF-AT components define a family of transcription factors targeted in T-cell activation. |journal=Nature |volume=369 |issue= 6480 |pages= 497-502 |year= 1994 |pmid= 8202141 |doi= 10.1038/369497a0 }}
* {{cite journal | vauthors = Di Somma MM, Majolini MB, Burastero SE, Telford JL, Baldari CT | title = Cyclosporin A sensitivity of the HIV-1 long terminal repeat identifies distinct p56lck-dependent pathways activated by CD4 triggering | journal = European Journal of Immunology | volume = 26 | issue = 9 | pages = 2181–2188 | date = Sep 1996 | pmid = 8814265 | doi = 10.1002/eji.1830260933 }}
*{{cite journal | author=Jain J, McCaffrey PG, Miner Z, ''et al.'' |title=The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun. |journal=Nature |volume=365 |issue= 6444 |pages= 352-5 |year= 1993 |pmid= 8397339 |doi= 10.1038/365352a0 }}
* {{cite journal | vauthors = Copeland KF, McKay PJ, Rosenthal KL | title = Suppression of the human immunodeficiency virus long terminal repeat by CD8+ T cells is dependent on the NFAT-1 element | journal = AIDS Research and Human Retroviruses | volume = 12 | issue = 2 | pages = 143–148 | date = Jan 1996 | pmid = 8834464 | doi = 10.1089/aid.1996.12.143 }}
*{{cite journal | author=Luo C, Burgeon E, Carew JA, ''et al.'' |title=Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes. |journal=Mol. Cell. Biol. |volume=16 |issue= 7 |pages= 3955-66 |year= 1996 |pmid= 8668213 |doi= }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
*{{cite journal | author=Di Somma MM, Majolini MB, Burastero SE, ''et al.'' |title=Cyclosporin A sensitivity of the HIV-1 long terminal repeat identifies distinct p56lck-dependent pathways activated by CD4 triggering. |journal=Eur. J. Immunol. |volume=26 |issue= 9 |pages= 2181-8 |year= 1996 |pmid= 8814265 |doi= }}
* {{cite journal | vauthors = Hodge MR, Chun HJ, Rengarajan J, Alt A, Lieberson R, Glimcher LH | title = NF-AT-Driven interleukin-4 transcription potentiated by NIP45 | journal = Science | volume = 274 | issue = 5294 | pages = 1903–1905 | date = Dec 1996 | pmid = 8943202 | doi = 10.1126/science.274.5294.1903 }}
*{{cite journal | author=Copeland KF, McKay PJ, Rosenthal KL |title=Suppression of the human immunodeficiency virus long terminal repeat by CD8+ T cells is dependent on the NFAT-1 element. |journal=AIDS Res. Hum. Retroviruses |volume=12 |issue= 2 |pages= 143-8 |year= 1996 |pmid= 8834464 |doi= }}
* {{cite journal | vauthors = Lyakh L, Ghosh P, Rice NR | title = Expression of NFAT-family proteins in normal human T cells | journal = Molecular and Cellular Biology | volume = 17 | issue = 5 | pages = 2475–84 | date = May 1997 | pmid = 9111316 | pmc = 232096 | doi =  }}
*{{cite journal | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791-806 |year= 1997 |pmid= 8889548 |doi= }}
* {{cite journal | vauthors = Amasaki Y, Masuda ES, Imamura R, Arai K, Arai N | title = Distinct NFAT family proteins are involved in the nuclear NFAT-DNA binding complexes from human thymocyte subsets | journal = Journal of Immunology | volume = 160 | issue = 5 | pages = 2324–33 | date = Mar 1998 | pmid = 9498773 | doi =  }}
*{{cite journal | author=Hodge MR, Chun HJ, Rengarajan J, ''et al.'' |title=NF-AT-Driven interleukin-4 transcription potentiated by NIP45. |journal=Science |volume=274 |issue= 5294 |pages= 1903-5 |year= 1997 |pmid= 8943202 |doi=  }}
* {{cite journal | vauthors = Chen L, Glover JN, Hogan PG, Rao A, Harrison SC | title = Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA | journal = Nature | volume = 392 | issue = 6671 | pages = 42–48 | date = Mar 1998 | pmid = 9510247 | doi = 10.1038/32100 }}
*{{cite journal | author=Lyakh L, Ghosh P, Rice NR |title=Expression of NFAT-family proteins in normal human T cells. |journal=Mol. Cell. Biol. |volume=17 |issue= 5 |pages= 2475-84 |year= 1997 |pmid= 9111316 |doi=  }}
*{{cite journal | author=Amasaki Y, Masuda ES, Imamura R, ''et al.'' |title=Distinct NFAT family proteins are involved in the nuclear NFAT-DNA binding complexes from human thymocyte subsets. |journal=J. Immunol. |volume=160 |issue= 5 |pages= 2324-33 |year= 1998 |pmid= 9498773 |doi=  }}
*{{cite journal  | author=Chen L, Glover JN, Hogan PG, ''et al.'' |title=Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. |journal=Nature |volume=392 |issue= 6671 |pages= 42-8 |year= 1998 |pmid= 9510247 |doi= 10.1038/32100 }}
}}
{{refend}}
{{refend}}


== External links ==
== External links ==
* {{MeshName|NFATC2+protein,+human}}
* {{MeshName|NFATC2+protein,+human}}
* [http://www.jauliaclab.com/]


{{PDB Gallery|geneid=4773}}
{{Transcription factors|g4}}
{{NLM content}}
{{NLM content}}
{{protein-stub}}
 
{{Transcription factors}}
{{DEFAULTSORT:Nfatc2}}
[[Category:Transcription factors]]
[[Category:Transcription factors]]
{{WikiDoc Sources}}
[[Category:Human proteins]]

Revision as of 00:23, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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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

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]

Interactions

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

References

  1. ↑ Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP, Admon A, Crabtree GR (Jun 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".
  3. ↑ Jauliac S, López-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A (Jul 2002). "The role of NFAT transcription factors in integrin-mediated carcinoma invasion". Nature Cell Biology. 4 (7): 540–4. doi:10.1038/ncb816. PMID 12080349.
  4. ↑ Yoeli-Lerner M, Yiu GK, Rabinovitz I, Erhardt P, Jauliac S, Toker A (Nov 2005). "Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT". Molecular Cell. 20 (4): 539–50. doi:10.1016/j.molcel.2005.10.033. PMID 16307918.
  5. ↑ Gaudineau B, Fougère M, Guaddachi F, Lemoine F, de la Grange P, Jauliac S (Oct 2012). "Lipocalin 2, the TNF-like receptor TWEAKR and its ligand TWEAK act downstream of NFAT1 to regulate breast cancer cell invasion". Journal of Cell Science. 125 (Pt 19): 4475–86. doi:10.1242/jcs.099879. PMID 22767506.
  6. ↑ Szuhai K, Ijszenga M, de Jong D, Karseladze A, Tanke HJ, Hogendoorn PC (Apr 2009). "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. doi:10.1158/1078-0432.CCR-08-2184. PMID 19318479.
  7. ↑ Youn HD, Chatila TA, Liu JO (Aug 2000). "Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis". The EMBO Journal. 19 (16): 4323–31. doi:10.1093/emboj/19.16.4323. PMC 302027. PMID 10944115.
  8. ↑ García-Rodríguez C, Rao A (Jun 1998). "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. doi:10.1084/jem.187.12.2031. PMC 2212364. PMID 9625762.
  9. ↑ Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH (Apr 2002). "Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression". The Journal of Experimental Medicine. 195 (8): 1003–12. doi:10.1084/jem.20011128. PMC 2193700. PMID 11956291.
  10. ↑ San-Antonio B, Iñiguez MA, Fresno M (Jul 2002). "Protein kinase Czeta phosphorylates nuclear factor of activated T cells and regulates its transactivating activity". The Journal of Biological Chemistry. 277 (30): 27073–80. doi:10.1074/jbc.M106983200. PMID 12021260.

Further reading

External links

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