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DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B

Overexpression of the Dual-specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) gene contributes to the retardation, craniofacial anomalies, cognitive impairment, and learning and memory deficits associated with Down Syndrome (DS). DCAF7/HAN11/WDR68 (hereafter WDR68) binds DYRK1A and is...

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Autores principales: Yousefelahiyeh, Mina, Xu, Jingyi, Alvarado, Estibaliz, Yu, Yang, Salven, David, Nissen, Robert M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264848/
https://www.ncbi.nlm.nih.gov/pubmed/30496304
http://dx.doi.org/10.1371/journal.pone.0207779
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author Yousefelahiyeh, Mina
Xu, Jingyi
Alvarado, Estibaliz
Yu, Yang
Salven, David
Nissen, Robert M.
author_facet Yousefelahiyeh, Mina
Xu, Jingyi
Alvarado, Estibaliz
Yu, Yang
Salven, David
Nissen, Robert M.
author_sort Yousefelahiyeh, Mina
collection PubMed
description Overexpression of the Dual-specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) gene contributes to the retardation, craniofacial anomalies, cognitive impairment, and learning and memory deficits associated with Down Syndrome (DS). DCAF7/HAN11/WDR68 (hereafter WDR68) binds DYRK1A and is required for craniofacial development. Accumulating evidence suggests DYRK1A-WDR68 complexes enable proper growth and patterning of multiple organ systems and suppress inappropriate cell growth/transformation by regulating the balance between proliferation and differentiation in multiple cellular contexts. Here we report, using engineered mouse C2C12 and human HeLa cell lines, that WDR68 is required for normal levels of DYRK1A. However, Wdr68 does not significantly regulate Dyrk1a mRNA expression levels and proteasome inhibition did not restore DYRK1A in cells lacking Wdr68 (Δwdr68 cells). Overexpression of WDR68 increased DYRK1A levels while overexpression of DYRK1A had no effect on WDR68 levels. We further report that WDR68 is similarly required for normal levels of the closely related DYRK1B kinase and that both DYRK1A and DYRK1B are essential for the transition from proliferation to differentiation in C2C12 cells. These findings reveal an additional role of WDR68 in DYRK1A-WDR68 and DYRK1B-WDR68 complexes.
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spelling pubmed-62648482018-12-19 DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B Yousefelahiyeh, Mina Xu, Jingyi Alvarado, Estibaliz Yu, Yang Salven, David Nissen, Robert M. PLoS One Research Article Overexpression of the Dual-specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) gene contributes to the retardation, craniofacial anomalies, cognitive impairment, and learning and memory deficits associated with Down Syndrome (DS). DCAF7/HAN11/WDR68 (hereafter WDR68) binds DYRK1A and is required for craniofacial development. Accumulating evidence suggests DYRK1A-WDR68 complexes enable proper growth and patterning of multiple organ systems and suppress inappropriate cell growth/transformation by regulating the balance between proliferation and differentiation in multiple cellular contexts. Here we report, using engineered mouse C2C12 and human HeLa cell lines, that WDR68 is required for normal levels of DYRK1A. However, Wdr68 does not significantly regulate Dyrk1a mRNA expression levels and proteasome inhibition did not restore DYRK1A in cells lacking Wdr68 (Δwdr68 cells). Overexpression of WDR68 increased DYRK1A levels while overexpression of DYRK1A had no effect on WDR68 levels. We further report that WDR68 is similarly required for normal levels of the closely related DYRK1B kinase and that both DYRK1A and DYRK1B are essential for the transition from proliferation to differentiation in C2C12 cells. These findings reveal an additional role of WDR68 in DYRK1A-WDR68 and DYRK1B-WDR68 complexes. Public Library of Science 2018-11-29 /pmc/articles/PMC6264848/ /pubmed/30496304 http://dx.doi.org/10.1371/journal.pone.0207779 Text en © 2018 Yousefelahiyeh et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yousefelahiyeh, Mina
Xu, Jingyi
Alvarado, Estibaliz
Yu, Yang
Salven, David
Nissen, Robert M.
DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B
title DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B
title_full DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B
title_fullStr DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B
title_full_unstemmed DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B
title_short DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B
title_sort dcaf7/wdr68 is required for normal levels of dyrk1a and dyrk1b
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264848/
https://www.ncbi.nlm.nih.gov/pubmed/30496304
http://dx.doi.org/10.1371/journal.pone.0207779
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