Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells
dc.bibliographicCitation.issue | 3 | eng |
dc.bibliographicCitation.journalTitle | Cell Death and Disease | eng |
dc.bibliographicCitation.volume | 3 | |
dc.contributor.author | Sanges, C. | |
dc.contributor.author | Scheuermann, C. | |
dc.contributor.author | Zahedi, R.P. | |
dc.contributor.author | Sickmann, A. | |
dc.contributor.author | Lamberti, A. | |
dc.contributor.author | Migliaccio, N. | |
dc.contributor.author | Baljuls, A. | |
dc.contributor.author | Marra, M. | |
dc.contributor.author | Zappavigna, S. | |
dc.contributor.author | Reinders, J. | |
dc.contributor.author | Rapp, U. | |
dc.contributor.author | Abbruzzese, A. | |
dc.contributor.author | Caraglia, M. | |
dc.contributor.author | Arcari, P. | |
dc.date.accessioned | 2018-02-19T09:50:09Z | |
dc.date.available | 2019-06-28T08:33:10Z | |
dc.date.issued | 2012 | |
dc.description.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. | |
dc.description.version | publishedVersion | eng |
dc.format | application/pdf | |
dc.identifier.uri | https://doi.org/10.34657/1734 | |
dc.identifier.uri | https://oa.tib.eu/renate/handle/123456789/3682 | |
dc.language.iso | eng | eng |
dc.publisher | London : Nature Publishing Group | |
dc.relation.doi | https://doi.org/10.1038/cddis.2012.16 | |
dc.rights.license | CC BY-NC-ND 3.0 Unported | eng |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ | eng |
dc.subject.ddc | 610 | |
dc.subject.other | Apoptosis | eng |
dc.subject.other | Cell signalling | eng |
dc.subject.other | Phosphorylation | eng |
dc.subject.other | Ubiquitylation | eng |
dc.title | Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells | |
dc.type | Article | eng |
dc.type | Text | eng |
tib.accessRights | openAccess | eng |
wgl.contributor | ISAS | eng |
wgl.subject | Medizin, Gesundheit | eng |
wgl.type | Zeitschriftenartikel | eng |
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