Nuclear factor of activated T cells contains Fos and Jun
- 1 April 1992
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 356 (6372), 801-804
- https://doi.org/10.1038/356801a0
Abstract
THE nuclear factor NF-AT (ref. 1) is induced in T cells stimulated through the T-cell receptor/CD3 complex, and is required for interleukin-2 (IL-2) gene induction. Although NF-AT has not been cloned or purified, there is evidence that it is a major target for immunosuppression by cyclosporin A (CsA) and FK506 (refs 2-7). NF-AT induction may require two activation-dependent events: the CsA-sensitive translocation of a pre-existing component and the CsA-resistant synthesis of a nuclear component8. Here we report that the newly synthesized nuclear component of NF-AT is the transcription factor AP-1. We show that the inducible nuclear form of NF-AT contains Fos and Jun proteins. Furthermore, we identify a pre-existing NF-AT-binding factor that is present in hypotonic extracts of unstimulated T cells. On the basis of binding, reconstitution and cotransfection experiments, we propose that activation of NF-AT occurs in at least two stages: a CsA-sensitive stage involving modification and/or translocation of the preexisting NF-AT complex, and a CsA-insensitive stage involving the addition of newly synthesized Fos or Fos/Jun proteins to the pre-existing complex.This publication has 28 references indexed in Scilit:
- The AP-1 site at -150 bp, but not the NF-kappa B site, is likely to represent the major target of protein kinase C in the interleukin 2 promoter.The Journal of Experimental Medicine, 1992
- Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin ANature, 1991
- G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartmentCell, 1991
- Chemistry and Biology of the Immunophilins and Their Immunosuppressive LigandsScience, 1991
- Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin.Proceedings of the National Academy of Sciences of the United States of America, 1990
- Transcription Factor Interactions: Selectors of Positive or Negative Regulation from a Single DNA ElementScience, 1990
- Transcriptional interference between c-Jun and the glucocorticoid receptor: Mutual inhibition of DNA binding due to direct protein-protein interactionCell, 1990
- Cyclosporin A Specifically Inhibits Function of Nuclear Proteins Involved in T Cell ActivationScience, 1989
- Identification of a Putative Regulator of Early T Cell Activation GenesScience, 1988
- Activation specificity of arsonate-reactive T cell clones. Structural requirements for hapten recognition and comparison with monoclonal antibodies.The Journal of Experimental Medicine, 1984