Nuclear factor of activated T cells contains Fos and Jun

Nature. 1992 Apr 30;356(6372):801-4. doi: 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 component. 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 pre-existing NF-AT complex, and a CsA-insensitive stage involving the addition of newly synthesized Fos or Fos/Jun proteins to the pre-existing complex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Binding, Competitive
  • Chloramphenicol / metabolism
  • Cyclosporine / pharmacology
  • Humans
  • Mice
  • Molecular Sequence Data
  • Proto-Oncogene Proteins c-fos / physiology*
  • Proto-Oncogene Proteins c-jun / physiology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transfection

Substances

  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Chloramphenicol
  • Cyclosporine