Título:
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p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes
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Autor/a:
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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
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Otros autores:
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Universitat de Barcelona |
Abstract:
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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. |
Materia(s):
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-Mitosi -Bioinformàtica -Expressió gènica -Mitosis -Bioinformatics -Gene expression |
Derechos:
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cc-by (c) Ferrándiz, N. et al., 2012
http://creativecommons.org/licenses/by/3.0/es |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Public Library of Science (PLoS)
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