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

Yousang Gwack, Sonia Sharma, Julie Nardone, Bogdan Tanasa, Alina Iuga, Sonal Srikanth, Heidi Okamura, Diana Bolton, Stefan Feske, Patrick G. Hogan and Anjana Rao ()
Additional contact information
Yousang Gwack: The CBR Institute for Biomedical Research
Sonia Sharma: The CBR Institute for Biomedical Research
Julie Nardone: The CBR Institute for Biomedical Research
Bogdan Tanasa: The CBR Institute for Biomedical Research
Alina Iuga: The CBR Institute for Biomedical Research
Sonal Srikanth: The CBR Institute for Biomedical Research
Heidi Okamura: The CBR Institute for Biomedical Research
Diana Bolton: The CBR Institute for Biomedical Research
Stefan Feske: The CBR Institute for Biomedical Research
Patrick G. Hogan: The CBR Institute for Biomedical Research
Anjana Rao: The CBR Institute for Biomedical Research

Nature, 2006, vol. 441, issue 7093, 646-650

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.

Date: 2006
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DOI: 10.1038/nature04631

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