To access the full text documents, please follow this link: http://hdl.handle.net/2445/33727

p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes
Ferrándiz, N.; Caraballo, J.M.; García-Gutierrez, L.; Devgan, V.; Rodríguez-Paredes, M.; Lafita, M.C.; Bretones, G.; Quintanilla, A.; Muñoz-Alonso, M.J.; Blanco, R.; Reyes, J.C.; Agell i Jané, Neus; Delgado, M.D.; Dotto, G.P.; León, J.
Universitat de Barcelona
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.
Mitosi
Bioinformàtica
Expressió gènica
Mitosis
Bioinformatics
Gene expression
cc-by (c) Ferrándiz, N. et al., 2012
http://creativecommons.org/licenses/by/3.0/es
Article
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

Show full item record

Related documents

Other documents of the same author

Rosell Polo, Joan Ramon; Arnó Satorra, Jaume; Vallès, Josep Maria; Llorens Calveras, Jordi; Blanco, R.; Palacín Roca, Jordi; Sanz Cortiella, Ricardo; Masip Vilalta, Joan; Ribes-Dasi, Manel
Costelli, Paola; García Martínez, Celia; Llovera i Tomàs, Marta; Carbó Carbó, Maria Neus; López-Soriano, Francisco J.; Agell i Jané, Neus; Tessitore, Luciana; Baccino, Francesco M.; Argilés Huguet, Josep Ma.
Costelli, Paola; García Martínez, Celia; Llovera i Tomàs, Marta; Carbó Carbó, Maria Neus; López-Soriano, Francisco J.; Agell i Jané, Neus; Tessitore, Luciana; Baccino, Francesco M.; Argilés Huguet, Josep Ma.
Agell i Jané, Neus; Aligué i Alemany, Rosa Maria; Bachs Valldeneu, Oriol
 

Coordination

 

Supporters