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A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT

Author

Listed:
  • Yousang Gwack

    (The CBR Institute for Biomedical Research
    Harvard Medical School)

  • Sonia Sharma

    (The CBR Institute for Biomedical Research
    Harvard Medical School)

  • Julie Nardone

    (The CBR Institute for Biomedical Research
    Cell Signaling Technology
    AVEO Pharmaceuticals Inc.
    University of Washington)

  • Bogdan Tanasa

    (The CBR Institute for Biomedical Research)

  • Alina Iuga

    (The CBR Institute for Biomedical Research
    Harvard Medical School)

  • Sonal Srikanth

    (The CBR Institute for Biomedical Research
    Harvard Medical School)

  • Heidi Okamura

    (The CBR Institute for Biomedical Research
    Harvard Medical School
    Cell Signaling Technology
    AVEO Pharmaceuticals Inc.)

  • Diana Bolton

    (The CBR Institute for Biomedical Research
    Cell Signaling Technology
    AVEO Pharmaceuticals Inc.
    University of Washington)

  • Stefan Feske

    (The CBR Institute for Biomedical Research
    Harvard Medical School)

  • Patrick G. Hogan

    (The CBR Institute for Biomedical Research)

  • Anjana Rao

    (The CBR Institute for Biomedical Research
    Harvard Medical School)

Abstract

Down's syndrome Down's syndrome is caused by an extra chromosome; somehow a 1.5-fold increase in the dosage of a gene or genes on chromosome 21 causes the wide-reaching effects associated with the condition. A study using ‘knockout’ mice now identifies two genes as candidates for involvement. A 1.5-fold increase in dosage of DSCR1 and DYRK1a destabilizes the regulation of signalling pathways involving the NFAT transcription factor. The discovery follows the surprise finding that NFATc1-4 and calcineurin mutant mice demonstrate nearly all the characteristics of Down's syndrome. In an unrelated paper, a genome-wide RNAi screen reveals conserved regulators of NFAT in Drosophila. NFAT is a purely vertebrate transcription factor, but this work breaks new ground by using Drosophila cells to study the function of a protein artificially introduced from a mammalian species. Pathways regulating the subcellular localization of NFAT proteins are strongly conserved across species and this new approach can identify new regulators of a transcription factor normally expressed in vertebrates.

Suggested Citation

  • Yousang Gwack & Sonia Sharma & Julie Nardone & Bogdan Tanasa & Alina Iuga & Sonal Srikanth & Heidi Okamura & Diana Bolton & Stefan Feske & Patrick G. Hogan & Anjana Rao, 2006. "A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT," Nature, Nature, vol. 441(7093), pages 646-650, June.
  • Handle: RePEc:nat:nature:v:441:y:2006:i:7093:d:10.1038_nature04631
    DOI: 10.1038/nature04631
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