%0 Journal Article
%A Salazar Roa, María
%A Lorente Pérez, María Del Mar
%A Garcia-Taboada, Elena
%A Pérez Gómez, Eduardo
%A Davila, Davila
%A Zuñiga, Patricia
%A Flores Landeira, Juana María
%A Rodriguez, Antonio
%A Hegedus, Zoltán
%A Mosen-Ansorena, David
%A Aransay, Ana María
%A Hernandez-Tiedra, Sonia
%A Lopez-Valero, Israël
%A Quintanilla, Miguel
%A Sánchez García, María Cristina
%A Iovanna, Juan
%A Dusetti, Nelson
%A Guzmán Pastor, Manuel
%A Francis, Sheila
%A Carracedo, Arkaitz
%A Kiss-Toth, Endre
%A Velasco Díez, Guillermo
%T Loss of Tribbles pseudokinase-3 promotes Akt-driven tumorigenesis via FOXO inactivation
%D 2014
%@ 1350-9047
%U https://hdl.handle.net/20.500.14352/96199
%X 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
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