RT Journal Article SR Electronic T1 Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation JF Science JO Science FD American Association for the Advancement of Science SP 1617 OP 1620 DO 10.1126/science.2595372 VO 246 IS 4937 A1 Emmel, EA A1 Verweij, CL A1 Durand, DB A1 Higgins, KM A1 Lacy, E A1 Crabtree, GR YR 1989 UL http://science.sciencemag.org/content/246/4937/1617.abstract 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.