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

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Abstract
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 calcineurin1–3. NFAT, a DNA-binding protein required for interleukin-2 gene transcription, is a potential target for calcineurin, cyclosporin A and FK5064–11. 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 cells9,11. Here we report that NFATp is a DNA-binding phosphoprotein of relative molecular mass ∼ 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.

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