Interferon α (IFNα) induces both apoptosis and a counteracting EGFErk-dependent survival response in cancer cells. In this report, IFNα increased eukaryotic Elongation Factor 1A (eEF-1A) protein expression by inhibition of eEF-1A degradation via a proteasome-dependent pathway. The reduction of the expression level of eEF-1A by RNA interference enhanced the apoptosis induced by IFNα on the same cells. Moreover, IFNα induced the phosphorylation of both serine and threonine in eEF-1A. These effects were paralleled by an increased co-immunoprecipitation and co-localization of eEF-1A with C-Raf. The suppression of C-Raf kinase activity with the inhibitor BAY 43-9006 completely antagonized the increase of both eEF-1A phosphorylation and expression and of C-Raf/eEF-1A co-localization induced by IFNα and enhanced apoptosis and eEF-1A ubiquitination. The dynamic simulation of 3D-structure of eEF-1A identified putative serine and threonine phosphorylation sites. In conclusion, the interaction between eEF-1A and CRaf increases eEF-1A stability and induces a survival activity.

C-Raf antagonizes apoptosis induced by INF-a in human lung cancer cells by phosphorylation and increase of the intracellular content of elongation factor 1A

LAMBERTI, ANNALISA;ARCARI, PAOLO;
2007

Abstract

Interferon α (IFNα) induces both apoptosis and a counteracting EGFErk-dependent survival response in cancer cells. In this report, IFNα increased eukaryotic Elongation Factor 1A (eEF-1A) protein expression by inhibition of eEF-1A degradation via a proteasome-dependent pathway. The reduction of the expression level of eEF-1A by RNA interference enhanced the apoptosis induced by IFNα on the same cells. Moreover, IFNα induced the phosphorylation of both serine and threonine in eEF-1A. These effects were paralleled by an increased co-immunoprecipitation and co-localization of eEF-1A with C-Raf. The suppression of C-Raf kinase activity with the inhibitor BAY 43-9006 completely antagonized the increase of both eEF-1A phosphorylation and expression and of C-Raf/eEF-1A co-localization induced by IFNα and enhanced apoptosis and eEF-1A ubiquitination. The dynamic simulation of 3D-structure of eEF-1A identified putative serine and threonine phosphorylation sites. In conclusion, the interaction between eEF-1A and CRaf increases eEF-1A stability and induces a survival activity.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/109796
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