The product of this gene is a member of the nuclear factors 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. Other members of this family of nuclear factors of activated T cells also participate in the formation of this complex. The product of this gene plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of the IL-2 and IL-4.[2]
NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation. Indeed, NFAT3 (NFATc4) is an inhibitor of cell motility by blocking the expression of LCN2.[3]
↑Hoey T, Sun YL, Williamson K, Xu X (May 1995). "Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins". Immunity. 2 (5): 461–72. doi:10.1016/1074-7613(95)90027-6. PMID7749981.
↑Fougère M, Gaudineau B, Barbier J, Guaddachi F, Feugeas JP, Auboeuf D, Jauliac S (Apr 2010). "NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene". Oncogene. 29 (15): 2292–301. doi:10.1038/onc.2009.499. PMID20101218.
↑Yang T, Davis RJ, Chow CW (Oct 2001). "Requirement of two NFATc4 transactivation domains for CBP potentiation". The Journal of Biological Chemistry. 276 (43): 39569–76. doi:10.1074/jbc.M102961200. PMID11514544.
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.
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.
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.
Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, Grant SR, Olson EN (Apr 1998). "A calcineurin-dependent transcriptional pathway for cardiac hypertrophy". Cell. 93 (2): 215–28. doi:10.1016/S0092-8674(00)81573-1. PMID9568714.
Aramburu J, Garcia-Cózar F, Raghavan A, Okamura H, Rao A, Hogan PG (Apr 1998). "Selective inhibition of NFAT activation by a peptide spanning the calcineurin targeting site of NFAT". Molecular Cell. 1 (5): 627–37. doi:10.1016/S1097-2765(00)80063-5. PMID9660947.
Graef IA, Chen F, Chen L, Kuo A, Crabtree GR (Jun 2001). "Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature". Cell. 105 (7): 863–75. doi:10.1016/S0092-8674(01)00396-8. PMID11439183.
Yang T, Davis RJ, Chow CW (Oct 2001). "Requirement of two NFATc4 transactivation domains for CBP potentiation". The Journal of Biological Chemistry. 276 (43): 39569–76. doi:10.1074/jbc.M102961200. PMID11514544.
Bennasser Y, Badou A, Tkaczuk J, Bahraoui E (Nov 2002). "Signaling pathways triggered by HIV-1 Tat in human monocytes to induce TNF-alpha". Virology. 303 (1): 174–80. doi:10.1006/viro.2002.1676. PMID12482669.
Graef IA, Wang F, Charron F, Chen L, Neilson J, Tessier-Lavigne M, Crabtree GR (May 2003). "Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons". Cell. 113 (5): 657–70. doi:10.1016/S0092-8674(03)00390-8. PMID12787506.
Lahti AL, Manninen A, Saksela K (May 2003). "Regulation of T cell activation by HIV-1 accessory proteins: Vpr acts via distinct mechanisms to cooperate with Nef in NFAT-directed gene expression and to promote transactivation by CREB". Virology. 310 (1): 190–6. doi:10.1016/S0042-6822(03)00164-8. PMID12788643.
