NFATC2

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Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Protein NFATC2 PDB 1a02.png
PDB rendering based on 1a02.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NFATC2 ; NFAT1; NFATP
External IDs OMIM600490 MGI102463 HomoloGene7861 ChEMBL: 4120 GeneCards: NFATC2 Gene
Orthologs
Species Human Mouse
Entrez 4773 18019
Ensembl ENSG00000101096 ENSMUSG00000027544
UniProt Q13469 Q60591
RefSeq (mRNA) NM_001136021 NM_001037177
RefSeq (protein) NP_001129493 NP_001032254
Location (UCSC) Chr 20:
50 – 50.18 Mb
Chr 2:
168.48 – 168.6 Mb
PubMed search [1] [2]

Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the NFATC2 gene.[1]

Function[edit]

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[edit]

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[edit]

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

References[edit]

  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". 
  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. 
  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. 
  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 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 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. 
  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. 
  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. 
  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. 
  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. 

Further reading[edit]

External links[edit]

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