@article{10902/1085,
year = {2012},
month = {5},
url = {http://hdl.handle.net/10902/1085},
abstract = {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.},
organization = {This study was supported by grants SAF08-01581 and ISCIII-RETIC RD06/0020/0017 from the Spanish Ministerio de Ciencia e Innovacion (MICINN) to JL; FIS 08/0829 to MDD; BFU2008-00238 and CSD2006-00049 from MICINN, and P06-CVI-4844 from Junta de Andalucı´a to JCR. NF was the recipient of a postdoctoral fellowship of the University of Cantabria. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of manuscript.},
publisher = {Public Library of Science},
publisher = {PLoS One, 2012, 7(5), e37759},
title = {P21 as a transcriptional co-repressor of S-phase and mitotic control genes},
author = {Ferrándiz Díaz, Nuria and Caraballo Otero, Juan Manuel and García Gutiérrez, Lucía and Devgan, Vikram and Rodriguez Paredes, Manuel and Lafita Navarro, María Carmen and Bretones Sánchez, Gabriel and Quintanilla Cavia, Andrea and Muñoz Alonso, María José and Blanco Fernández, Rosa and Reyes, José Carlos and Agell, Neus and Delgado Villar, María Dolores and Dotto, Gian Paolo and León Serrano, Javier},
}