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Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc

Author

Listed:
  • Scot A. Wolfe

    (Harvard University)

  • Pei Zhou

    (Harvard University)

  • Volker Dötsch

    (Harvard Medical School)

  • Lin Chen

    (Harvard University)

  • Angie You

    (Harvard University)

  • Steffan N. Ho

    (Stanford University Medical School)

  • Gerald R. Crabtree

    (Stanford University Medical School)

  • Gerhard Wagner

    (Harvard Medical School)

  • Gregory L. Verdine

    (Harvard University)

Abstract

TRANSCRIPTION factors of the NFAT family regulate the production of effector proteins that coordinate the immune response1. The immunosuppressive drugs FK506 and cyclosporin A (CsA) act by blocking a Ca2+-mediated signalling pathway leading to NFAT. Although FK506 and CsA have enabled human organs to be transplanted routinely, the toxic side-effects of these drugs limit their usage. This toxicity might be absent in antagonists that target NFAT directly. As a first step in the structure-based search for NFAT antagonists, we now report the identification and solution structure of a 20K domain of NFATc (NFATc-DBD) that is both necessary and sufficient to bind DNA and activate transcription cooperatively. Although the overall fold of the NFATc DNA-binding domain is related to that of NF-κB p50 (refs 2, 3), the two proteins use significantly different strategies for DNA recognition. On the basis of these results, we present a model for the cooperative complex formed between NFAT and the mitogenic transcription factor AP-1 on the interleukin-2 enhancer.

Suggested Citation

  • Scot A. Wolfe & Pei Zhou & Volker Dötsch & Lin Chen & Angie You & Steffan N. Ho & Gerald R. Crabtree & Gerhard Wagner & Gregory L. Verdine, 1997. "Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc," Nature, Nature, vol. 385(6612), pages 172-176, January.
    • Handle: RePEc:nat:nature:v:385:y:1997:i:6612:d:10.1038_385172a0
    DOI: 10.1038/385172a0
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