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| Título: | Loss of Tribbles pseudokinase-3 promotes Akt-driven tumorigenesis via FOXO inactivation |
Autor: | Salazar, María CSIC; Pérez-Gómez, Eduardo CSIC ORCID CVN; Flores, Juana María; Quintanilla, Miguel CSIC ORCID; Sánchez, Cristina; Carracedo, Ángel; Velasco, Guillermo | Fecha de publicación: | 2015 | Editor: | Nature Publishing Group | Citación: | Cell Death and Differentiation 22(1): 131-144 (2015) | Resumen: | Tribbles pseudokinase-3 (TRIB3) has been proposed to act as an inhibitor of AKT although the precise molecular basis of this activity and whether the loss of TRIB3 contributes to cancer initiation and progression remain to be clarified. In this study, by using a wide array of in vitro and in vivo approaches, including a Trib3 knockout mouse, we demonstrate that TRIB3 has a tumor-suppressing role. We also find that the mechanism by which TRIB3 loss enhances tumorigenesis relies on the dysregulation of the phosphorylation of AKT by the mTORC2 complex, which leads to an enhanced phosphorylation of AKT on Ser473 and the subsequent hyperphosphorylation and inactivation of the transcription factor FOXO3. These observations support the notion that loss of TRIB3 is associated with a more aggressive phenotype in various types of tumors by enhancing the activity of the mTORC2/AKT/FOXO axis. | Descripción: | et al. | Versión del editor: | http://dx.doi.org/10.1038/cdd.2014.133 | URI: | http://hdl.handle.net/10261/125015 | DOI: | 10.1038/cdd.2014.133 | Identificadores: | doi: 10.1038/cdd.2014.133 issn: 1350-9047 e-issn: 1476-5403 |
| Aparece en las colecciones: | (IIBM) Artículos |
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| Fichero | Descripción | Tamaño | Formato | |
|---|---|---|---|---|
| TRIBBLESPSEUDOKINASE.pdf | 2,63 MB | Adobe PDF |  Visualizar/Abrir |
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