Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes
- PMID: 8668213
- PMCID: PMC231392
- DOI: 10.1128/MCB.16.7.3955
Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes
Abstract
Transcription factors of the NFAT family play a key role in the transcription of cytokine genes and other genes during the immune response. We have identified two new isoforms of the transcription factor NFAT1 (previously termed NFATp) that are the predominant isoforms expressed in murine and human T cells. When expressed in Jurkat T cells, recombinant NFAT1 is regulated, as expected, by the calmodulin-dependent phosphatase calcineurin, and its function is inhibited by the immunosuppressive agent cyclosporin A (CsA). Transactivation by recombinant NFAT1 in Jurkat T cells requires dual stimulation with ionomycin and phorbol 12-myristate 13-acetate; this activity is potentiated by coexpression of constitutively active calcineurin and is inhibited by CsA. Immunocytochemical analysis indicates that recombinant NFAT1 localizes in the cytoplasm of transiently transfected T cells and translocates into the nucleus in a CsA-sensitive manner following ionomycin stimulation. When expressed in COS cells, however, NFAT1 is capable of transactivation, but it is not regulated correctly: its subcellular localization and transcriptional function are not affected by stimulation of the COS cells with ionomycin and phorbol 12-myristate 13-acetate. Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response.
Similar articles
-
Identification and characterization of a novel nuclear factor of activated T-cells-1 isoform expressed in mouse brain.J Biol Chem. 2001 Apr 27;276(17):14350-8. doi: 10.1074/jbc.M007854200. Epub 2001 Jan 24. J Biol Chem. 2001. PMID: 11278367
-
Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes.J Biol Chem. 1998 Apr 17;273(16):9544-51. doi: 10.1074/jbc.273.16.9544. J Biol Chem. 1998. PMID: 9545284
-
Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis.EMBO J. 2000 Aug 15;19(16):4323-31. doi: 10.1093/emboj/19.16.4323. EMBO J. 2000. PMID: 10944115 Free PMC article.
-
NFATp, a cyclosporin-sensitive transcription factor implicated in cytokine gene induction.J Leukoc Biol. 1995 Apr;57(4):536-42. doi: 10.1002/jlb.57.4.536. J Leukoc Biol. 1995. PMID: 7722411 Review.
-
Transcription factors of the NFAT family: regulation and function.Annu Rev Immunol. 1997;15:707-47. doi: 10.1146/annurev.immunol.15.1.707. Annu Rev Immunol. 1997. PMID: 9143705 Review.
Cited by
-
Cell cycle and apoptosis regulation by NFAT transcription factors: new roles for an old player.Cell Death Dis. 2016 Apr 21;7(4):e2199. doi: 10.1038/cddis.2016.97. Cell Death Dis. 2016. PMID: 27100893 Free PMC article. Review.
-
MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells.EMBO J. 2000 Oct 16;19(20):5387-95. doi: 10.1093/emboj/19.20.5387. EMBO J. 2000. PMID: 11032806 Free PMC article.
-
Integration of intermittent calcium signals in T cells revealed by temporally patterned optogenetics.iScience. 2023 Jan 26;26(2):106068. doi: 10.1016/j.isci.2023.106068. eCollection 2023 Feb 17. iScience. 2023. PMID: 36824271 Free PMC article.
-
Regulation of calcineurin by growth cone calcium waves controls neurite extension.J Neurosci. 2000 Jan 1;20(1):315-25. doi: 10.1523/JNEUROSCI.20-01-00315.2000. J Neurosci. 2000. PMID: 10627609 Free PMC article.
-
Control of NFATx1 nuclear translocation by a calcineurin-regulated inhibitory domain.Mol Cell Biol. 1997 Apr;17(4):2066-75. doi: 10.1128/MCB.17.4.2066. Mol Cell Biol. 1997. PMID: 9121455 Free PMC article.
References
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
- Actions
- Actions
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases