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Deciphering DYRK1A Signaling using Proteomics and Transcriptomics
Author(s) -
Poss Zachary,
Ebmeier Christopher,
Simpson Helen,
Pagratis Maria,
McClureBegley Tristan,
Old William
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.662.22
Subject(s) - dyrk1a , trisomy , down syndrome , chromosome 21 , biology , phenotype , proteomics , transcriptome , gene , population , genetics , neuroscience , chromosome , gene expression , medicine , environmental health
Trisomy 21 is the most common genetic manifestation of intellectual disability, with deleterious brain phenotypes thought to be caused by increased dosage of critical genes on chromosome 21, including the kinase DYRK1A. Additionally, individuals with Down syndrome are at an increased risk of developing Alzheimer's disease, immune dysfunction and certain cancers, and DYRK1A has been implicated in each of these conditions. Although it is clear that DYRK1A is critical for neural development, little is known about the substrates it modifies and how its dosage and activity contribute to trisomy 21 phenotypes. We employed phosphoproteomic and transcriptomic approaches in a 3D neuronal model of the developing trisomy 21 brain and found that DYRK1A phosphorylates and regulates key factors involved in splicing and transcription regulation. As both of these processes are central to neural differentiation, these data suggest that DYRK1A activity may be critical for the transition from progenitor to differentiated neurons. Additionally, dysregulation of this transition may contribute to phenotypic brain hallmarks exhibited within the trisomy 21 population, which express an extra copy of DYRK1A. Support or Funding Information Linda Crnic Institute for Down Syndrome, Anna and John J. Sie Foundation, DARPA This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .