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Science 22 December 1989:
Vol. 246. no. 4937, pp. 1617 - 1620
DOI: 10.1126/science.2595372
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Articles

Science, Vol 246, Issue 4937, 1617-1620
Copyright © 1989 by American Association for the Advancement of Science

articles

Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation

EA Emmel, CL Verweij, DB Durand, KM Higgins, E Lacy, and GR Crabtree

Howard Hughes Medical Institute, Stanford University, CA 94305.

One action of cyclosporin A thought to be central to many of its immunosuppressive effects is its ability to inhibit the early events of T lymphocyte activation such as lymphokine gene transcription in response to signals initiated at the antigen receptor. Cyclosporin A was found to specifically inhibit the appearance of DNA binding activity of NF-AT, AP-3, and to a lesser extent NF-kappa B, nuclear proteins that appear to be important in the transcriptional activation of the genes for interleukin-2 and its receptor, as well as several other lymphokines. In addition, cyclosporin A abolished the ability of the NF-AT binding site to activate a linked promoter in transfected mitogen-stimulated T lymphocytes and in lymphocytes from transgenic mice. These results indicate that cyclosporin A either directly inhibits the function of nuclear proteins critical to T lymphocyte activation or inhibits the action of a more proximal member of the signal transmission cascade leading from the antigen receptor to the nucleus.


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Chemistry and biology of the immunophilins and their immunosuppressive ligands.
S. Schreiber (1991)
Science 251, 283-287
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Regulation of gene expression with double-stranded phosphorothioate oligonucleotides.
A Bielinska, R. Shivdasani, L. Zhang, and G. Nabel (1990)
Science 250, 997-1000
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Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor..
S Fiering, J P Northrop, G P Nolan, P S Mattila, G R Crabtree, and L A Herzenberg (1990)
Genes & Dev. 4, 1823-1834
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A cell culture model for T lymphocyte clonal anergy.
R. Schwartz (1990)
Science 248, 1349-1356
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Inhibition of FKBP rotamase activity by immunosuppressant FK506: twisted amide surrogate.
M. Rosen, R. Standaert, A Galat, M Nakatsuka, and S. Schreiber (1990)
Science 248, 863-866
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Lymphocytes: Window to the Future.
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Arch Surg 125, 665-667
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