Disease relevance of EEF1A1

• To generate specific tools for, in particular, localization studies of the eukaryotic elongation factor 1A (eEF1A), we have applied phage display in various formats to affinity-improve and map epitopes of two previously isolated, low-affinity single-chain Fv (scFv) G3 and D1 [1].
• In contrast, PTI-1 RNA is not detected in human melanoma, neuroblastoma, osteosarcoma, normal cerebellum, or glioblastoma multiforme cell lines [2].
• By using a pair of primers recognizing a 280-bp region within the 630-bp 5' PTI-1 sequence, reverse transcription-PCR detects PTI-1 expression in patient-derived prostate carcinomas but not in normal prostate or benign hypertrophic prostate tissue [2].
• A putative dominant-acting nude mouse prostatic carcinoma tumor-inducing gene, PTI-1, has been cloned that is expressed in patient-derived human prostatic carcinomas but not in benign prostatic hypertrophy or normal prostate tissue [2].
• The EFG1-mutant patient had early-onset Leigh syndrome, whereas the EFTu-mutant patient had severe infantile macrocystic leukodystrophy with micropolygyria [3].

High impact information on EEF1A1

• This rotation, driven by a conformational change in elongation factor Tu involving GTP hydrolysis, transorients the incoming tRNA into the A site from the D site of initial binding and decoding, where it can be proofread and accommodated [4].
• One of the unexpected cellular components found interacting with the cytoskeleton is elongation factor 1 alpha (EF-1alpha) [5].
• Exp5 stimulates nuclear export of eEF1A when microinjected into the nucleus of Xenopus laevis oocytes [6].
• Taken together, we show that there exists an alternative tRNA export pathway which can be exploited to keep eEF1A out of the cell nucleus [6].
• This cargo-exportin interaction is rather un usual in that eEF1A binds the exportin not directly, but instead via aminoacylated tRNAs [7].

Chemical compound and disease context of EEF1A1

• This interaction is mediated not only by MA, but also by the nucleocapsid domain, which provides a second, independent EF1alpha-binding site on the Gag polyprotein [8].
• An inventory of amino acid sequences around the guanine-nucleotide-binding site in elongation factor Tu from Escherichia coli and homologous amino acid sequences in G proteins, initiation and elongation factors and proteins from the RAS family shows two regions containing conserved sequence elements [9].
• A tRNA containing a long extra arm, namely E. coli tRNA(Leu1) has been crosslinked to elongation factor Tu, with the crosslinking reagent trans-diamminedichloroplatinum(II) [10].
• Overexpression of ribosomal proteins L4 and L5 and the putative alternative elongation factor PTI-1 in the doxorubicin resistant human colon cancer cell line LoVoDxR [11].
• Translation elongation factor EF-1 alpha became stably associated with potato tuber polysomes at the onset of hypoxia, coincident with a sharp rise in lactate and decrease in tissue pH [12].

Biological context of EEF1A1

• The aptameric oligonucleotides GT were found to exert a selective, specific and dose-dependent cell growth inhibition effect on a variety of human cancer cells by recognising specific nuclear proteins and among these in particular an isoform of the eukaryotic elongation factor 1A1 (EEF1A1) [13].
• Screening a human prostatic carcinoma (LNCaP) cDNA library with a 214-bp DNA fragment found by DD permitted the cloning of a full-length 2.0-kb PTI-1 cDNA [2].
• Sequence analysis indicates that PTI-1 is a gene containing a 630-bp 5' sequence and a 3' sequence homologous to a truncated and mutated form of human elongation factor 1 alpha [2].
• These results indicate that PTI-1 may be a member of a class of oncogenes that could affect protein translation and contribute to carcinoma development in human prostate and other tissues [2].
• Fluorescence resonance energy transfer was used to observe aminoacyl-tRNA (aa-tRNA) stably accommodating into the aminoacyl site (A site) of the ribosome via a multistep, elongation factor-Tu dependent process [14].

Anatomical context of EEF1A1

• In eukaryotic cells the concentration of EF-1 alpha exceeds that of the complex beta gamma delta by a factor of 5-10 [15].
• Apparently, the common characteristic of these GTPases is an extensive consensus structural unit that possibly accounts for a similar interaction with the ribosome and is composed of two domains homologous to the G domain and domain II in EF-Tu and EF-G [16].
• Over-expression of either EFTu or EFTs in control and patient fibroblasts produced dominant negative effects, indicating that the relative abundance of these factors is an important determinant of translation efficiency [17].
• We discuss the possible role of EF-Tumt chaperone activity in protein quality control in mitochondria, with regard to the recently reported in vivo chaperone function of eEF1A [18].
• Retinol-regulated gene expression in human tracheobronchial epithelial cells. Enhanced expression of elongation factor EF-1 alpha [19].

Associations of EEF1A1 with chemical compounds

• Subsequent analysis identified the translation elongation factor, eEF1A, and its guanine nucleotide exchange factor, eEF1Bbeta, as TCTP-interacting partners [20].
• This novel posttranslational modification may represent an important alteration of EF-1 alpha, comparable to the regulatory effects of posttranslational methylation of EF-1 alpha lysine residues [21].
• EF-1 beta gamma decreases the amount of EF-1 alpha required for polyphenylalanine synthesis about 20-fold [22].
• Although entry of the charged transfer messenger RNA (tmRNA) into the ribosome proceeded in the absence of elongation factor (EF-Tu) and in the presence of EF-Tu and the antibiotic kirromycin, evidence was found for the involvement of EF-Tu in trans-translation initiation [23].
• Metabolic radiolabeling with [3H] ethanolamine shows that, in all cells examined, EF-1 alpha is the major radiolabeled protein [21].

Physical interactions of EEF1A1

• We have identified eukaryotic elongation factor 1A (eEF1A) and tRNA as RanGTP-dependent binding partners of exportin-5 (Exp5) [6].
• In vitro and in vivo studies confirmed that TCTP bound specifically eEF1Bbeta and eEF1A [20].
• Identification of the sites in the eukaryotic elongation factor 1 alpha involved in the binding of elongation factor 1 beta and aminoacyl-tRNA [24].
• Asp83 has a conformation similar to the conformation of the corresponding residue in the EF-Tu/EF-Ts complex [25].

Regulatory relationships of EEF1A1

• EF-1 beta gamma enhances the ability to EF-1 alpha to support the binding of Phe-tRNA to the ribosomes and enhances the GTPase activity of EF-1 alpha [22].
• Association of the 5'HS4 sequence of the chicken beta-globin locus control region with human EF1 alpha gene promoter induces ubiquitous and high expression of human CD55 and CD59 cDNAs in transgenic rabbits [26].
• To evaluate enzyme replacement therapy for GSD II patients, we have expressed human GAA cDNA in Chinese hamster ovary-K1 cells utilising a vector that places the cDNA under the transcriptional control of the human polypeptide chain elongation factor 1 alpha gene promoter [27].

Other interactions of EEF1A1

• Additionally, MS analysis also identified eEF1A as a TCTP interactor [20].
• Two differentially expressed isoforms of eEF1A, designated eEF1A-1 and eEF1A-2, are found in mammals [28].
• Two candidate genes, EEF1A1 and IMPG1, were selected from the region between D6S280 and D6S1644 markers where the families are linked [29].
• It can also export the RNA binding proteins ILF3 and elongation factor EF1A [30].
• Southern analysis indicates that EF-1 beta in the human genome, like EF-1 alpha, appears to be specified by more than one gene [31].

Analytical, diagnostic and therapeutic context of EEF1A1

• Probing Northern blots with a DNA fragment corresponding to the 5' region of PTI-1 identifies multiple PTI-1 transcripts in RNAs from human carcinoma cell lines derived from the prostate, lung, breast, and colon [2].
• By using molecular cloning, we have shown that one of the effects of retinol on cultured human tracheobronchial epithelial (HTBE) cells is the enhancement (from 2- to 4-fold) of the mRNA encoding the elongation factor EF-1 alpha [19].
• Genomic Southern blot analysis revealed at least twenty loci in the human genome with sequence homology to the EF-1 alpha cDNA [32].
• Protein synthesis elongation factor Tu has been mapped on the surface of the ribosome by immunoelectron microscopy [33].
• We have mapped the functional EEF1A gene to 6q14 by combined fluorescence in situ hybridization (FISH) and PCR analysis of a somatic cell hybrid panel and mapped EEF1A2 to 20q13.3 by FISH [34].

References