ArticleCell death & disease2012
Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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16 citing papers in PubMed, 47 citations in OpenAlex.
- A web portal for exploring kinase-substrate interactions.NPJ systems biology and applications · 2024Article
- Article
- GBAS Regulates the Proliferation and Metastasis of Ovarian Cancer Cells by Combining with eEF1A1.The oncologist · 2022Article
- Mutational analysis reveals potential phosphorylation sites in eukaryotic elongation factor 1A that are important for its activity.FEBS letters · 2021Article
- On the Need to Tell Apart Fraternal Twins eEF1A1 and eEF1A2, and Their Respective Outfits.International journal of molecular sciences · 2021Review
- Hepatitis B Virus DNA Polymerase Displays an Anti-Apoptotic Effect by Interacting with Elongation Factor-1 Alpha-2 in Hepatoma Cells.Journal of microbiology and biotechnology · 2021Article
- SNX16 activates c-Myc signaling by inhibiting ubiquitin-mediated proteasomal degradation of eEF1A2 in colorectal cancer development.Molecular oncology · 2020Article
- Identification of a Specific Translational Machinery via TCTP-EF1A2 Interaction Regulating NF1-associated Tumor Growth by Affinity Purification and Data-independent Mass Spectrometry Acquisition (AP-DIA).Molecular & cellular proteomics : MCP · 2019Article
- Signaling Pathways Involved in the Regulation of mRNA Translation.Molecular and cellular biology · 2018Review
- Regulation of eukaryotic elongation factor 1 alpha (eEF1A) by dynamic lysine methylation.RNA biology · 2018Article
- The novel lysine specific methyltransferase METTL21B affects mRNA translation through inducible and dynamic methylation of Lys-165 in human eukaryotic elongation factor 1 alpha (eEF1A).Nucleic acids research · 2017Article
- Overexpression of eukaryotic elongation factor 1 alpha-2 is associated with poorer prognosis in patients with gastric cancer.Journal of cancer research and clinical oncology · 2015Article
- Saccharomyces cerevisiae Eukaryotic Elongation Factor 1A (eEF1A) Is Methylated at Lys-390 by a METTL21-Like Methyltransferase.PloS one · 2015Article
- The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections.Frontiers in oncology · 2015Review
- Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes.Nucleic acids research · 2014Article
- Tumor suppressor p16(INK4a) inhibits cancer cell growth by downregulating eEF1A2 through a direct interaction.Journal of cell science · 2013Article
Corrections and comments
- Erratum issuedReinders, J [added]
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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