NFAT
Encyclopedia
Nuclear factor of activated T-cells (NFAT) is a general name applied to a family of transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

s shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the development of cardiac, skeletal muscle, and nervous systems.

The NFAT transcription factor family consists of five members NFATc1
NFATC1
Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the NFATC1 gene.-Further reading:- External links :...

, NFATc2
NFATC2
Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the NFATC2 gene.NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation...

, NFATc3
NFATC3
Nuclear factor of activated T-cells, cytoplasmic 3 is a protein that in humans is encoded by the NFATC3 gene.- External links :...

, NFATc4
NFATC4
Nuclear factor of activated T-cells, cytoplasmic 4 is a protein that in humans is encoded by the NFATC4 gene.NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation...

, and NFAT5
NFAT5
Nuclear factor of activated T-cells 5, also known as NFAT5, is a human gene that encodes a transcription factor that regulates the expression of genes involved in the osmotic stress....

. NFATc1 through NFATc4 are regulated by calcium signaling. Calcium signaling is critical to NFAT activation because calmodulin
Calmodulin
Calmodulin is a calcium-binding protein expressed in all eukaryotic cells...

 (CaM), a well-known calcium sensor protein, activates the serine/threonine phosphatase calcineurin
Calcineurin
Calcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B . It activates the T cells of the immune system and can be blocked by drugs...

 (CN). Activated CN rapidly dephosphorylates the serine-rich region (SRR) and SP-repeats in the amino termini of NFAT proteins, resulting in a conformational change that exposes a nuclear localization signal, resulting in NFAT nuclear import. Nuclear import of NFAT proteins is opposed by maintenance kinases in the cytoplasm and export kinases in the nucleus. Export kinases, such as PKA and GSK-3β, must be inactivated for NFAT nuclear retention. NFAT proteins have weak DNA binding capacity. Therefore, to effectively bind DNA, NFAT proteins must cooperate with other nuclear resident transcription factors generically referred to as NFATn. This important feature of NFAT transcription factors enables integration and coincidence detection of calcium signals with other signaling pathways such as ras-MAPK or PKC. In addition, this signaling integration is involved in tissue-specific gene expression during development. A screen of ncRNA sequences identified in EST
Expressed sequence tag
An expressed sequence tag or EST is a short sub-sequence of a cDNA sequence. They may be used to identify gene transcripts, and are instrumental in gene discovery and gene sequence determination. The identification of ESTs has proceeded rapidly, with approximately 65.9 million ESTs now available in...

 sequencing projects discovered a 'ncRNA repressor of the nuclear factor of activated T cells' called NRON
NRON
NRON also known as ncRNA repressor of the nuclear factor of activated T cells is a non-coding RNA involved in repressing NFAT. The function of this ncRNA was identified by a large-scale screen of 512 non-coding RNAs discovered in earlier EST sequencing projects.Each of the RNAs that were conserved...

.


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) and NFAT5 are pro-invasive and pro-migratory in breast carcinoma and NFAT3 (NFATc4) is an inhibitor of cell motility .
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