The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun

Nature. 1993 Sep 23;365(6444):352-5. doi: 10.1038/365352a0.


Transcription of lymphokine genes in activated T cells is inhibited by the immunosuppressive agents cyclosporin A and FK506, which act by blocking the phosphatase activity of calcineurin. NFAT, a DNA-binding protein required for interleukin-2 gene transcription, is a potential target for calcineurin, cyclosporin A and FK506. NFAT contains a subunit (NFATp) which is present in unstimulated T cells and which forms a complex with Fos and Jun proteins in the nucleus of activated T cells. Here we report that NFATp is a DNA-binding phosphoprotein of relative molecular mass approximately 120,000 and is a substrate for calcineurin in vitro. Purified NFATp forms DNA-protein complexes with recombinant Jun homodimers or Jun-Fos heterodimers; the DNA-binding domains of Fos and Jun are essential for the formation of the NFATp-Fos-Jun-DNA complex. The interaction between the lymphoid-specific factor NFATp and the ubiquitous transcription factors Fos and Jun provides a novel mechanism for combinatorial regulation of interleukin-2 gene transcription, which integrates the calcium-dependent and the protein-kinase C-dependent pathways of T-cell activation.

Publication types

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

MeSH terms

  • Animals
  • Calcineurin
  • Calmodulin-Binding Proteins / metabolism*
  • Cell Line, Transformed
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism*
  • Interleukin-2 / genetics
  • Mice
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphoproteins / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • T-Lymphocytes / metabolism
  • Transcription Factors / metabolism*


  • Calmodulin-Binding Proteins
  • DNA-Binding Proteins
  • Interleukin-2
  • NFATC Transcription Factors
  • NFATC2 protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Recombinant Proteins
  • Transcription Factors
  • DNA
  • Calcineurin
  • Phosphoprotein Phosphatases