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| Título: | P21 as a transcriptional co-repressor of S-phase and mitotic control genes |
Autor: | Ferrándiz, Nuria CSIC; Caraballo, Juan M. CSIC; García-Gutiérrez, Lucía CSIC ORCID; Rodríguez-Paredes, Manuel CSIC; Lafita, M. Carmen CSIC ORCID; Bretones, Gabriel CSIC ORCID; Quintanilla, Andrea CSIC; Muñoz-Alonso, María J. CSIC; Blanco, Rosa CSIC; Reyes, José C. CSIC ORCID ; Delgado, M. Dolores CSIC ORCID; León, Javier CSIC ORCID CVN | Fecha de publicación: | 2012 | Editor: | Public Library of Science | Citación: | PLoS ONE 7(5): e37759 (2012) | Resumen: | It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes. | Descripción: | This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al. | Versión del editor: | http://dx.doi.org/10.1371/journal.pone.0037759 | URI: | http://hdl.handle.net/10261/56344 | DOI: | 10.1371/journal.pone.0037759 | ISSN: | 1932-6203 |
| Aparece en las colecciones: | (IIBM) Artículos (IBBTEC) Artículos (CABIMER) Artículos |
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| p21 as a Transcriptional.pdf | 1,17 MB | Adobe PDF |  Visualizar/Abrir |
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