NFATC1 explained

Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the NFATC1 gene.^[1]

Function

The product of this gene is a component of the nuclear factor of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation, and an inducible nuclear component. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as ciclosporin. Five transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes.^[2]

Interactions

NFATC1 has been shown to interact with PIM1.^[3]

See also

• NFAT

Further reading

• Rao A, Luo C, Hogan PG . Transcription factors of the NFAT family: regulation and function . Annual Review of Immunology . 15 . 707–47 . 1997 . 9143705 . 10.1146/annurev.immunol.15.1.707 .
• Crabtree GR . Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT . Cell . 96 . 5 . 611–4 . Mar 1999 . 10089876 . 10.1016/S0092-8674(00)80571-1 . 8817053 . free .
• Horsley V, Pavlath GK . NFAT: ubiquitous regulator of cell differentiation and adaptation . The Journal of Cell Biology . 156 . 5 . 771–4 . Mar 2002 . 11877454 . 2173310 . 10.1083/jcb.200111073 .
• Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M . HIV/SIV escape from immune surveillance: focus on Nef . Current HIV Research . 2 . 2 . 141–51 . Apr 2004 . 15078178 . 10.2174/1570162043484924 .
• Li X, Ho SN, Luna J, Giacalone J, Thomas DJ, Timmerman LA, Crabtree GR, Francke U . Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp . Cytogenetics and Cell Genetics . 68 . 3–4 . 185–91 . 1995 . 7842733 . 10.1159/000133910 .
• Jabado N, Le Deist F, Fisher A, Hivroz C . 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 . European Journal of Immunology . 24 . 11 . 2646–52 . Nov 1994 . 7957556 . 10.1002/eji.1830241112 . 30435577 .
• Vacca A, Farina M, Maroder M, Alesse E, Screpanti I, Frati L, Gulino A . 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 . Biochemical and Biophysical Research Communications . 205 . 1 . 467–74 . Nov 1994 . 7999066 . 10.1006/bbrc.1994.2689 .
• Park J, Takeuchi A, Sharma S . Characterization of a new isoform of the NFAT (nuclear factor of activated T cells) gene family member NFATc . The Journal of Biological Chemistry . 271 . 34 . 20914–21 . Aug 1996 . 8702849 . 10.1074/jbc.271.34.20914 . free .
• Di Somma MM, Majolini MB, Burastero SE, Telford JL, Baldari CT . Cyclosporin A sensitivity of the HIV-1 long terminal repeat identifies distinct p56lck-dependent pathways activated by CD4 triggering . European Journal of Immunology . 26 . 9 . 2181–8 . Sep 1996 . 8814265 . 10.1002/eji.1830260933 . 23430217 .
• Beals CR, Sheridan CM, Turck CW, Gardner P, Crabtree GR . Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3 . Science . 275 . 5308 . 1930–4 . Mar 1997 . 9072970 . 10.1126/science.275.5308.1930 . 22590899 .
• Kinoshita S, Su L, Amano M, Timmerman LA, Kaneshima H, Nolan GP . The T cell activation factor NF-ATc positively regulates HIV-1 replication and gene expression in T cells . Immunity . 6 . 3 . 235–44 . Mar 1997 . 9075924 . 10.1016/S1074-7613(00)80326-X . free .
• Zhou P, Sun LJ, Dötsch V, Wagner G, Verdine GL . Solution structure of the core NFATC1/DNA complex . Cell . 92 . 5 . 687–96 . Mar 1998 . 9506523 . 10.1016/S0092-8674(00)81136-8 . 16009648 . free .
• Kinoshita S, Chen BK, Kaneshima H, Nolan GP . Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells . Cell . 95 . 5 . 595–604 . Nov 1998 . 9845362 . 10.1016/S0092-8674(00)81630-X . 17954556 . free .
• Chuvpilo S, Zimmer M, Kerstan A, Glöckner J, Avots A, Escher C, Fischer C, Inashkina I, Jankevics E, Berberich-Siebelt F, Schmitt E, Serfling E . Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells . Immunity . 10 . 2 . 261–9 . Feb 1999 . 10072078 . 10.1016/S1074-7613(00)80026-6 . free .
• Chuvpilo S, Avots A, Berberich-Siebelt F, Glöckner J, Fischer C, Kerstan A, Escher C, Inashkina I, Hlubek F, Jankevics E, Brabletz T, Serfling E . Multiple NF-ATc isoforms with individual transcriptional properties are synthesized in T lymphocytes . Journal of Immunology . 162 . 12 . 7294–301 . Jun 1999 . 10.4049/jimmunol.162.12.7294 . 10358178 . 26133892 . free .
• Wang JK, Kiyokawa E, Verdin E, Trono D . The Nef protein of HIV-1 associates with rafts and primes T cells for activation . Proceedings of the National Academy of Sciences of the United States of America . 97 . 1 . 394–9 . Jan 2000 . 10618429 . 26674 . 10.1073/pnas.97.1.394 . 2000PNAS...97..394W . free .
• Porter CM, Havens MA, Clipstone NA . Identification of amino acid residues and protein kinases involved in the regulation of NFATc subcellular localization . The Journal of Biological Chemistry . 275 . 5 . 3543–51 . Feb 2000 . 10652349 . 10.1074/jbc.275.5.3543 . free .

Notes and References

1. Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP, Admon A, Crabtree GR . NF-AT components define a family of transcription factors targeted in T-cell activation . Nature . 369 . 6480 . 497–502 . Jun 1994 . 8202141 . 10.1038/369497a0 . 1994Natur.369..497N . 9920546 .
2. Web site: Entrez Gene: NFATC1 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1.
3. Rainio EM, Sandholm J, Koskinen PJ . Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase . Journal of Immunology . 168 . 4 . 1524–7 . Feb 2002 . 11823475 . 10.4049/jimmunol.168.4.1524 . free .