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]
↑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. PMID8202141.
↑Rainio EM, Sandholm J, Koskinen PJ (Feb 2002). "Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase". Journal of Immunology. 168 (4): 1524–7. doi:10.4049/jimmunol.168.4.1524. PMID11823475.
Further reading
Rao A, Luo C, Hogan PG (1997). "Transcription factors of the NFAT family: regulation and function". Annual Review of Immunology. 15: 707–47. doi:10.1146/annurev.immunol.15.1.707. PMID9143705.
Crabtree GR (Mar 1999). "Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT". Cell. 96 (5): 611–4. doi:10.1016/S0092-8674(00)80571-1. PMID10089876.
Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M (Apr 2004). "HIV/SIV escape from immune surveillance: focus on Nef". Current HIV Research. 2 (2): 141–51. doi:10.2174/1570162043484924. PMID15078178.
Li X, Ho SN, Luna J, Giacalone J, Thomas DJ, Timmerman LA, Crabtree GR, Francke U (1995). "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. doi:10.1159/000133910. PMID7842733.
Jabado N, Le Deist F, Fisher A, Hivroz C (Nov 1994). "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. doi:10.1002/eji.1830241112. PMID7957556.
Vacca A, Farina M, Maroder M, Alesse E, Screpanti I, Frati L, Gulino A (Nov 1994). "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. doi:10.1006/bbrc.1994.2689. PMID7999066.
Park J, Takeuchi A, Sharma S (Aug 1996). "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. doi:10.1074/jbc.271.34.20914. PMID8702849.
Di Somma MM, Majolini MB, Burastero SE, Telford JL, Baldari CT (Sep 1996). "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. doi:10.1002/eji.1830260933. PMID8814265.
Beals CR, Sheridan CM, Turck CW, Gardner P, Crabtree GR (Mar 1997). "Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3". Science. 275 (5308): 1930–4. doi:10.1126/science.275.5308.1930. PMID9072970.
Kinoshita S, Su L, Amano M, Timmerman LA, Kaneshima H, Nolan GP (Mar 1997). "The T cell activation factor NF-ATc positively regulates HIV-1 replication and gene expression in T cells". Immunity. 6 (3): 235–44. doi:10.1016/S1074-7613(00)80326-X. PMID9075924.
Zhou P, Sun LJ, Dötsch V, Wagner G, Verdine GL (Mar 1998). "Solution structure of the core NFATC1/DNA complex". Cell. 92 (5): 687–96. doi:10.1016/S0092-8674(00)81136-8. PMID9506523.
Kinoshita S, Chen BK, Kaneshima H, Nolan GP (Nov 1998). "Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells". Cell. 95 (5): 595–604. doi:10.1016/S0092-8674(00)81630-X. PMID9845362.
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 (Feb 1999). "Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells". Immunity. 10 (2): 261–9. doi:10.1016/S1074-7613(00)80026-6. PMID10072078.
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 (Jun 1999). "Multiple NF-ATc isoforms with individual transcriptional properties are synthesized in T lymphocytes". Journal of Immunology. 162 (12): 7294–301. PMID10358178.
Porter CM, Havens MA, Clipstone NA (Feb 2000). "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. doi:10.1074/jbc.275.5.3543. PMID10652349.