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.
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Jain, J., McCaffrey, P., Valge-Archer, V. et al. Nuclear factor of activated T cells contains Fos and Jun. Nature 356, 801–804 (1992). https://doi.org/10.1038/356801a0
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DOI: https://doi.org/10.1038/356801a0
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