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Title: | p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes |
Author: | Ferrándiz, Nuria Caraballo, Juan M. García-Gutierrez, Lucia Devgan, Vikram Rodríguez-Paredes, Manuel Lafita, M. Carmen Bretones, Gabriel Quintanilla, Andrea Muñoz-Alonso, M. José Blanco, Rosa Reyes, José C. Agell i Jané, Neus Delgado, M. Dolores Dotto, G. Paolo León, Javier |
Keywords: | Mitosi Bioinformàtica Expressió gènica Mitosis Bioinformatics Gene expression |
Issue Date: | 25-May-2012 |
Publisher: | Public Library of Science (PLoS) |
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. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0037759 |
It is part of: | PLoS One, 2012, vol. 7, num. 5, p. e37759 |
URI: | http://hdl.handle.net/2445/33727 |
Related resource: | http://dx.doi.org/10.1371/journal.pone.0037759 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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