Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/81101
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | c-Myc inhibits ras-mediated differentiation of pheochromocytoma cells by blocking c-Jun up-regulation |
Autor: | Vaqué, José P. CSIC ORCID; Fernández-García, Belén; García-Sanz, Pablo CSIC; Ferrándiz, Nuria CSIC; Bretones, Gabriel CSIC ORCID; Calvo, Fernando CSIC ORCID ; Crespo, Piero CSIC ORCID; Marín, M. Carmen; León, Javier CSIC ORCID CVN | Fecha de publicación: | 2008 | Editor: | American Association for Cancer Research | Citación: | Molecular Cancer Research 6(2): 325-339 (2008) | Resumen: | Although mutant Ras proteins were originally described as transforming oncoproteins, they induce growth arrest, senescence, and/or differentiation in many cell types. c-Myc is an oncogenic transcription factor that cooperates with Ras in cellular transformation and oncogenesis. However, the Myc-Ras relationship in cellular differentiation is largely unknown. Here, we have analyzed the effects of c-Myc on PC12-derived cells (UR61 cell line), harboring an inducible N-Ras oncogene. In these cells, Ras activation induces neuronal-like differentiation by a process involving c-Jun activation. We found that c-Myc inhibited Ras-mediated differentiation by a mechanism that involves the blockade of c-Jun induction in response to Ras signal. Accordingly, ectopically expressed c-Jun could bypass c-Myc impediment of Ras-induced differentiation and activator protein 1 activation. Interestingly, it did not rescue the proliferative arrest elicited by Ras and did not enhance the differentiation-associated apoptosis. The blockade of Ras-mediated induction of c-Jun takes place at the level of c-Jun proximal promoter. Mutational analysis revealed that c-Myc regions involved in DNA binding and transactivation are required to block differentiation and c-Jun induction. c-Myc does not seem to require Miz-1 to inhibit differentiation and block c-Jun induction. Furthermore, Max is not required for c-Myc activity, as UR61 cells lack a functional Max gene. c-Myc-inhibitory effect on the Ras/c-Jun connection is not restricted to UR61 cells as it can occur in other cell types as K562 or HEK293. In conclusion, we describe a novel interplay between c-Myc and c-Jun that controls the ability of Ras to trigger the differentiation program of pheochromocytoma cells. Copyright © 2008 American Association for Cancer Research. | URI: | http://hdl.handle.net/10261/81101 | DOI: | 10.1158/1541-7786.MCR-07-0180 | Identificadores: | doi: 10.1158/1541-7786.MCR-07-0180 issn: 1541-7786 e-issn: 1557-3125 |
Aparece en las colecciones: | (IBBTEC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
31
checked on 24-abr-2024
WEB OF SCIENCETM
Citations
30
checked on 28-feb-2024
Page view(s)
991
checked on 23-abr-2024
Download(s)
107
checked on 23-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.