Nuclear factor of activated T cells contains Fos and Jun.
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.
Jain
J
J
Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
McCaffrey
P G
PG
Valge-Archer
V E
VE
Rao
A
A
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002701:Chloramphenicol / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014162:Transfection
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D002701:Chloramphenicol; D016572:Cyclosporine