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.