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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/33727
p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes
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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.
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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. p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes. _PLoS One_. 2012. Vol. 7, núm. 5, pàgs. e37759. [consulta: 25 de gener de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/33727]