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  • Title: The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun.
    Author: Jain J, McCaffrey PG, Miner Z, Kerppola TK, Lambert JN, Verdine GL, Curran T, Rao A.
    Journal: Nature; 1993 Sep 23; 365(6444):352-5. PubMed ID: 8397339.
    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 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.
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