Recombinant NFAT1 (NFATp) Is Regulated by Calcineurin in T Cells and Mediates Transcription of Several Cytokine Genes

作者: C Luo , E Burgeon , J A Carew , P G McCaffrey , T M Badalian

DOI: 10.1128/MCB.16.7.3955

关键词: Interleukin 2COS cellsPromoterMolecular biologyNFATC Transcription FactorsSTAT4Jurkat cellsBiologyTranscription factorNFAT

摘要: Transcription factors of the NFAT family play a key role in transcription cytokine genes and other during immune response. We have identified two new isoforms factor NFAT1 (previously termed NFATp) that are predominant expressed murine human T cells. When Jurkat cells, recombinant is regulated, as expected, by calmodulin-dependent phosphatasecalcineurin,anditsfunctionisinhibitedbytheimmunosuppressiveagentcyclosporinA(CsA).Transactivation cells requires dual stimulation with ionomycin phorbol 12-myristate 13-acetate; this activity potentiated coexpression constitutively active calcineurin inhibited CsA. Immunocytochemical analysis indicates localizes cytoplasm transiently transfected translocates into nucleus CsA-sensitive manner following stimulation. COS however, capable transactivation, but it not regulated correctly: its subcellular localization transcriptional function affected 13-acetate. Recombinant can mediate interleukin-2, interleukin-4, tumor necrosis alpha, granulocyte-macrophage colonystimulating promoters suggesting contributes to these The nuclear activated (NFAT) was originallyidentifiedinTcellsasanessentialtranscriptionfactorfor

参考文章(65)
M L Schmitz, M A dos Santos Silva, H Altmann, M Czisch, T A Holak, P A Baeuerle, Structural and functional analysis of the NF-kappa B p65 C terminus. An acidic and modular transactivation domain with the potential to adopt an alpha-helical conformation. Journal of Biological Chemistry. ,vol. 269, pp. 25613- 25620 ,(1994) , 10.1016/S0021-9258(18)47294-8
P. S. Mattila, K. S. Ullman, S. Fiering, E. A. Emmel, M. McCutcheon, G. R. Crabtree, L. A. Herzenberg, The actions of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes The EMBO Journal. ,vol. 9, pp. 4425- 4433 ,(1990) , 10.1002/J.1460-2075.1990.TB07893.X
P.G. McCaffrey, B.A. Perrino, T.R. Soderling, A. Rao, NF-ATp, a T lymphocyte DNA-binding protein that is a target for calcineurin and immunosuppressive drugs. Journal of Biological Chemistry. ,vol. 268, pp. 3747- 3752 ,(1993) , 10.1016/S0021-9258(18)53757-1
N.R. Yaseen, A.L. Maizel, F. Wang, S. Sharma, Comparative analysis of NFAT (nuclear factor of activated T cells) complex in human T and B lymphocytes. Journal of Biological Chemistry. ,vol. 268, pp. 14285- 14293 ,(1993) , 10.1016/S0021-9258(19)85239-0
Francis J. Dumont, M. J. Tocci, P. Kwok, John Siekierka, K. A. Collier, Steven Degudicibus, C. Shirley Lin, Diana Matkovich, J. Chin, N. I. Hutchinson, The immunosuppressant FK506 selectively inhibits expression of early T cell activation genes. Journal of Immunology. ,vol. 143, pp. 718- 726 ,(1989)
Gourisankar Ghosh, Gregory Van Duyne, Sankar Ghosh, Paul B. Sigler, Structure of NF-kappa B p50 homodimer bound to a kappa B site. Nature. ,vol. 373, pp. 303- 310 ,(1998) , 10.1038/373303A0
J.P. Northrop, K.S. Ullman, G.R. Crabtree, Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex. Journal of Biological Chemistry. ,vol. 268, pp. 2917- 2923 ,(1993) , 10.1016/S0021-9258(18)53861-8
Lori E. Hutchinson, Michael A. McCloskey, FcϵRI-mediated Induction of Nuclear Factor of Activated T-cells Journal of Biological Chemistry. ,vol. 270, pp. 16333- 16338 ,(1995) , 10.1074/JBC.270.27.16333
P N Cockerill, D Bohmann, M F Shannon, F Jenkins, Multiple signals are required for function of the human granulocyte-macrophage colony-stimulating factor gene promoter in T cells. Journal of Immunology. ,vol. 155, pp. 1240- 1251 ,(1995)