PT  - JOURNAL ARTICLE
AU  - Emmel, EA
AU  - Verweij, CL
AU  - Durand, DB
AU  - Higgins, KM
AU  - Lacy, E
AU  - Crabtree, GR
TI  - Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation
AID  - 10.1126/science.2595372
DP  - 1989 Dec 22
TA  - Science
PG  - 1617--1620
VI  - 246
IP  - 4937
4099  - http://science.sciencemag.org/content/246/4937/1617.short
4100  - http://science.sciencemag.org/content/246/4937/1617.full
SO  - Science1989 Dec 22; 246
AB  - 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.