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

Nature volume 365, pages 352–355 (1993)Cite this article

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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Author notes

  1. Zoe Miner

    Present address: Centre for Nutrition and Medicine, New England Deaconess Hospital, 1 Autumn Street, Boston, Massachusetts, 02115, USA

Authors and Affiliations

  1. Division of Tumor Virology, Dana-Farber Cancer Institute,

    Jugnu Jain, Patricia G. McCafffrey, Zoe Miner & Anjana Rao

  2. Department of Pathology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Jugnu Jain, Patricia G. McCafffrey, Zoe Miner & Anjana Rao

  3. Department of Molecular Oncology and Virology, Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey, 07110, USA

    Tom K. Kerppola & Tom Curran

  4. Department of Chemistry, Harvard University, Cambridge, Massachusetts, 02138, USA

    John N. Lambert & Gregory L. Verdine

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  1. Jugnu Jain
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Jain, J., McCafffrey, P., Miner, Z. et al. The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun. Nature 365, 352–355 (1993). https://doi.org/10.1038/365352a0

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