학술논문

C-Raf antagonizes apoptosis induced by IFN-α in human lung cancer cells by phosphorylation and increase of the intracellular content of elongation factor 1A.
Document Type
Article
Source
Cell Death & Differentiation. May2007, Vol. 14 Issue 5, p952-962. 11p.
Subject
*APOPTOSIS
*EPIDERMAL growth factor
*CELL death
*EUKARYOTIC cells
*UBIQUITIN
*PHOSPHORYLATION
Language
ISSN
1350-9047
Abstract
Interferon α (IFNα) induces both apoptosis and a counteracting epidermal growth factor 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 colocalization 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 colocalization induced by IFNα and enhanced apoptosis and eEF-1A ubiquitination. Cell transfection with the mutated K48R ubiquitin increased EF-1A expression and desensitized tumor cells to the modulating effects of IFNα. The dynamic simulation of 3Dstructure of eEF-1A identified putative serine and threonine phosphorylation sites. In conclusion, the interaction between eEF-1A and C-Raf increases eEF-1A stability and induces a survival activity.Cell Death and Differentiation (2007) 14, 952–962. doi:10.1038/sj.cdd.4402102; published online 2 March 2007 [ABSTRACT FROM AUTHOR]