Please use this identifier to cite or link to this item:
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
Expressió gènica
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:
It is part of: PLoS One, 2012, vol. 7, num. 5, p. e37759
Related resource:
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Biomedicina)

Files in This Item:
File Description SizeFormat 
614382.pdf1.17 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons