English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/50201
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

Myc inhibits p27-induced erythroid differentiation of leukemia cells by repressing erythroid master genes without reversing p27-mediated cell cycle arrest

AuthorsAcosta, Juan C.; Ferrándiz, Nuria ; Bretones, Gabriel ; Torrano, Verónica; Blanco, Rosa ; Richard, C.; Delgado, M. Dolores ; León, Javier
Issue Date2008
PublisherAmerican Society for Microbiology
CitationMolecular and Cellular Biology 28(24): 7286-7295 (2008)
AbstractInhibition of differentiation has been proposed as an important mechanism for Myc-induced tumorigenesis, but the mechanisms involved are unclear. We have established a genetically defined differentiation model in human leukemia K562 cells by conditional expression of the cyclin-dependent kinase (Cdk) inhibitor p27 (inducible by Zn2+) and Myc (activatable by 4-hydroxy-tamoxifen). Induction of p27 resulted in erythroid differentiation, accompanied by Cdk inhibition and G1 arrest. Interestingly, activation of Myc inhibited p27-mediated erythroid differentiation without affecting p27-mediated proliferation arrest. Microarray-based gene expression indicated that, in the presence of p27, Myc blocked the upregulation of several erythroid-cell-specific genes, including NFE2, JUNB, and GATA1 (transcription factors with a pivotal role in erythropoiesis). Moreover, Myc also blocked the upregulation of Mad1, a transcriptional antagonist of Myc that is able to induce erythroid differentiation. Cotransfection experiments demonstrated that Myc-mediated inhibition of differentiation is partly dependent on the repression of Mad1 and GATA1. In conclusion, this model demonstrates that Myc-mediated inhibition of differentiation depends on the regulation of a specific gene program, whereas it is independent of p27-mediated cell cycle arrest. Our results support the hypothesis that differentiation inhibition is an important Myc tumorigenic mechanism that is independent of cell proliferation. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Publisher version (URL)http://dx.doi.org/10.1128/MCB.00752-08
URIhttp://hdl.handle.net/10261/50201
DOI10.1128/MCB.00752-08
Identifiersdoi: 10.1128/MCB.00752-08
issn: 0270-7306
Appears in Collections:(IBBTEC) Artículos
Files in This Item:
File Description SizeFormat 
Myc Inhibits p27-Induced.pdf1,18 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.