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Title: Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells
Authors: Sanges, C.Scheuermann, C.Zahedi, R. P.Sickmann, A.Lamberti, A.Migliaccio, N.Baljuls, A.Marra, M.Zappavigna, S.Rapp, U.Abbruzzese, A.Caraglia, M.Arcari, P.
Publishers Version: https://doi.org/10.1038/sj.bjc.6604387
Issue Date: 2012
Published in: Cell Death and Disease, Volume 3, Issue 3
Publisher: London : Nature Publishing Group
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.
Keywords: Apoptosis; Cell signalling; Phosphorylation; Ubiquitylation
DDC: 610
License: CC BY-NC-ND 3.0 Unported
Link to License: https://creativecommons.org/licenses/by-nc-nd/3.0/
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