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Title

Attenuation of Notch signalling by the Down-syndrome-associated kinase DYRK1A

AuthorsFernández-Martínez, Javier; Vela, Eva M.; Tora-Ponsioen, Mireille; Ocaña, Oscar H.; Nieto, M. Ángela ; Galcerán, Joan
KeywordsDevelopment
DYRK1A
Notch
Phosphorylation
Down syndrome
Issue Date21-Apr-2009
PublisherCompany of Biologists
CitationJournal of Cell Science 122: 1574-1583 (2009)
AbstractNotch signalling is used throughout the animal kingdom to spatially and temporally regulate cell fate, proliferation and differentiation. Its importance is reflected in the dramatic effects produced on both development and health by small variations in the strength of the Notch signal. The Down-syndrome-associated kinase DYRK1A is coexpressed with Notch in various tissues during embryonic development. Here we show that DYRK1A moves to the nuclear transcription compartment where it interacts with the intracellular domain of Notch promoting its phosphorylation in the ankyrin domain and reducing its capacity to sustain transcription. DYRK1A attenuates Notch signalling in neural cells both in culture and in vivo, constituting a novel mechanism capable of modulating different developmental processes that can also contribute to the alterations observed during brain development in animal models of Down syndrome.
Description10 pages.-- PMID: 19383720 [PubMed].-- Printed version published May 15, 2009.
Supporting information available at: http://jcs.biologists.org/cgi/content/full/122/10/1574/DC1
Publisher version (URL)http://dx.doi.org/10.1242/jcs.044354
URIhttp://hdl.handle.net/10261/17493
DOI10.1242/jcs.044354
ISSN0021-9533
Appears in Collections:(IN) Artículos
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