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Current Topics in Peptide & Protein Research   Volumes    Volume 8 
Functional role of translation elongation factor 1A in IFNα-induced apoptosis of human lung cancer cells
Annalisa Lamberti, Michele Caraglia, Olimpia Longo, Carmen Sanges, Monica Marra, Alberto Abbruzzese, Paolo Arcari
Pages: 51 - 60
Number of pages: 10
Current Topics in Peptide & Protein Research
Volume 8 

Copyright © 2007 Research Trends. All rights reserved

This article describes some functional properties of eukaryotic EF-1A, a core component of the protein synthesis machinery, at the onset of cell transformation. EF-1A is shown to be upregulated in cell death moreover, it seems to be involved in the regulation of ubiquitin-mediated protein degradation. In addition, EF-1A undergoes several post-translational modifications such as phospho-rylation and methylation that generally influence its activity. Here, the behavior of EF-1A in a hepidermoid cancer cell line (H1355) is reported. In these cells, interferon α (IFNα) induces both apoptosis and a counteracting EGF-->Erk-dependent survival response. Treatment of H1355 cells with IFNα increased EF-1A protein expression by inhibiting its degradation via proteasome-dependent pathway. In particular, the increment of EF-1A was mainly due to the EF-1A2 isoform rather than the EF-1A1 one. If the expression level of EF-1A was decreased by RNA interference, an enhanced apoptosis induced by IFNα was instead observed. In addition, treatment of H1355 cells with IFNα induced also both serine and threonine C-Raf-mediated phosphorylation of EF-1A. The suppression of C-Raf activity with BAY 43-9006 C-Raf inhibitor completely antagonized the increase of EF-1A expression and enhanced apoptosis induced by IFNα. In conclusion, the interaction between EF-1A and C-Raf increases EF-1A stability and induces a survival activity. These results suggest that the extra-translational roles of EF-1A could offer tools for cancer intervention.
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