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...

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Bibliographic Details
Published in:Nature (London) 1992-04, Vol.356 (6372), p.801-804
Main Authors: Jain, Jugnu, McCaffrey, Patricia G, Valge-Archer, Viia E, Rao, Anjana
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Binding, Competitive
Biological and medical sciences
Cellular biology
Chloramphenicol - metabolism
Cyclosporine - pharmacology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humanities and Social Sciences
Humans
Immunobiology
letter
Lymphoid organs: ontogeny, organization, homing phenomenon
Mice
Molecular Sequence Data
multidisciplinary
Proteins
Proto-Oncogene Proteins c-fos - physiology
Proto-Oncogene Proteins c-jun - physiology
Science
Science (multidisciplinary)
T-Lymphocytes, Helper-Inducer - immunology
Transfection
Translocation
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Summary: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 8 . 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.
ISSN:0028-0836
1476-4687
DOI:10.1038/356801a0