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

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" (PDF). 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

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


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