NDLI: Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sanges, C. Scheuermann, C. Zahedi, R. P. Sickmann, A. Lamberti, A. Migliaccio, N. Baljuls, A. Marra, M. Zappavigna, S. Reinders, J. Rapp, U. Abbruzzese, A. Caraglia, M. Arcari, P.
Description	Country affiliation: Italy Author Affiliation: Sanges C ( Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy.)
Abstract	We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated phosphorylation sites and defined their role in the regulation of eEF1A half-life and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. Interestingly, S21 belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt, in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D) mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It indicates that the blockage of S21 interferes with or even supports C-Raf induced apoptosis rather than cell survival. Raf-mediated regulation of this site could be a crucial mechanism involved in the functional switching of eEF1A between its role in protein biosynthesis and its participation in other cellular processes.
File Format	HTM / HTML
e-ISSN	20414889
DOI	10.1038/cddis.2012.16
Journal	Cell Death and Disease
Volume Number	3
Language	English
Publisher	Nature Publishing Group
Publisher Date	2012-03-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Research Support, Non-u.s. Gov't Phosphorylation Protein Multimerization Proto-oncogene Proteins B-raf Cos Cells Recombinant Proteins Cercopithecus Aethiops Transfection Phosphoproteins Genetics Peptide Elongation Factor 1 Protein Stability Protein Structure, Tertiary Signal Transduction Gene Expression Regulation Models, Molecular Metabolism Discipline Cell Biology Proto-oncogene Proteins C-raf Animals Protein Binding Mutation Apoptosis
Content Type	Text
Resource Type	Article

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