Nuclear DYRK1A :new insights into its role within the nucleus
The view on how protein kinases regulate gene expression have recently expanded to include not only transcription factors but also histones, chromatin remodelers or components of the basal transcription machinery, which are directly modified on genomic loci. For the shuttling kinase DYRK1A (dual-spe...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2013 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/283483 |
| Acceso en línea: | http://hdl.handle.net/10803/283483 |
| Access Level: | acceso abierto |
| Palabra clave: | Cell growth Crecimiento celular DYRK1A Interactome Interactoma Nucleus Núcleo Protein kinase Proteina quinasa RNA polymerase II RNA polimerasa II RNA polymerase III RNA polimerasa III Transcription Transcripción 577 |
| Sumario: | The view on how protein kinases regulate gene expression have recently expanded to include not only transcription factors but also histones, chromatin remodelers or components of the basal transcription machinery, which are directly modified on genomic loci. For the shuttling kinase DYRK1A (dual-specificity tyrosine-regulated kinase), most of its nuclear-associated functions can be explained by DYRK1A cytosolic activities, questioning a role for DYRK1A within the nuclear compartment. In the present study, through an unbiased proteomic approach the first “DYRK1A nuclear interactome” have been generated. DYRK1A interacts with several components of the basal transcriptional machinery as well as with the pre-mRNA processing machinery. Moreover, evidences uncovering a new role for DYRK1A as a transcriptional regulator of specific target genes have been generated. Genome-wide DYRK1A-chromatin analysis shows that the kinase is recruited to RNA polymerase II proximal promoters, via a highly conserved palindromic sequence, and also to RNA polymerase III-dependent promoters. Growth-dependent induction of the expression of a subset of target genes (protein coding and tRNAs) depends on DYRK1A protein levels and/or activity. In addition, downregulation of DYRK1A leads to a reduction in cell size. DYRK1A could therefore work by sitting on promoters of specific genes and act on different components of the basal transcription and/or mRNA processing machinery to modulate gene expression. |
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