Disease relevance of Eef1a2

• Mice bearing the autosomal recessive mutation 'wasted' (wst/wst) express a disease syndrome characterized by neurologic dysfunction, immunodeficiency, and increased sensitivity to the killing effects of ionizing radiation relative to normal littermates (wst/-) and to parental control mice (BCF1, BALB/c, and C57BL/6) [1].
• A quantitative S1 nuclease protection assay was used to compare the relative steady-state levels of eEF-Tu mRNA in total mRNA in total RNA isolated from hexamethylene-bisacetamide-induced murine erythroleukemia cells [2].
• Spleen cells from control and wasted (wst) mice, a putative animal model for the human genetic disease ataxia-telangiectasia, were tested for inhibition of replicative (semiconservative) DNA synthesis after treatments with bleomycin, gamma-irradiation, 4-nitroquinoline 1-oxide, and ultraviolet irradiation [3].
• Mice homozygous for the autosomal recessive mutation wasted (wst/wst) undergo a progressive wasting beginning at the third week of postnatal life, when body weight declines in the mutants [4].
• Reactive gliosis was observed at 19 days postnatal in wst/wst cervical spinal cord, showing a rostrocaudal gradient [5].

High impact information on Eef1a2

• Expression of Eef1a2 takes over from Eef1a in heart and muscle at precisely the time at which the wasted phenotype becomes manifest [6].
• In addition, studies of COS cells transfected with the S1 gene containing small changes around the first AUG suggest that bicistronic mRNA translation is regulated at the level of elongation [7].
• To determine if uninfected cells can utilize bicistronic genes, a bovine papilloma virus-based vector system was used to select mouse C127 cell lines containing multiple integrated copies of the reovirus S1 gene [7].
• Enzyme activity in wst/wst mice is reduced to 38% of that found in the erythrocytes from control mice, and the apparent Km for adenosine is reduced to 51% of control [8].
• The 5' end of the gene has been defined, both by nuclease S1 protection and primer extension studies and by a functional assay in which an HPRT minigene, capable of expression in cultured cells, was created by ligating the 5' end of the gene onto wild-type human HPRT cDNA [9].

Biological context of Eef1a2

• Mouse translation elongation factor eEF1A-2 interacts with Prdx-I to protect cells against apoptotic death induced by oxidative stress [10].
• Thus, our results suggest that eEF1A-2 interacts with Prdx-I to functionally provide cells with extraordinary resistance to oxidative stress-induced cell death [10].
• Adenosine deaminase, Ada, is in mouse chromosome 2H3, and is not allelic with wasted, wst [11].
• Peptide elongation factor eEF1A-2/S1 expression in cultured differentiated myotubes and its protective effect against caspase-3-mediated apoptosis [12].
• After activation with concanavalin A, however, splenocytes from wst/wst mice showed a lower percentage of cells in S phase compared with that in controls [1].

Anatomical context of Eef1a2

• In adult mammalian tissues, isoform eEF1A-1 is present in all tissues except neurons, cardiomyocytes, and myotubes, where its isoform, eEF1A-2, is the only form expressed [10].
• Here we show that Prdx-I coimmunoprecipitates with eEF1A-2 from extracts of both cultured cells and mouse tissues expressing this protein, but it does not do so with its isoform, eEF1A-1, even though the latter is abundantly present [10].
• Peptide elongation factor eEF1A-2/S1, which shares 92% homology with eEF1A-1/EF-1alpha, is exclusively expressed in brain, heart, and skeletal muscle [12].
• Comparison of two-dimensional gel electrophoresis patterns of proteins from wst/wst and control mouse thymus revealed that an acidic protein with a molecular mass of approximately 30 kDa was consistently expressed at lower levels in wasted mice than in controls [1].
• We report here the isolation of a full-length cDNA from a mouse brain library and a partial-length cDNA from a human hippocampus library which share extensive sequence similarity to rat S1 cDNA [13].

Associations of Eef1a2 with chemical compounds

• Quantitative solution hybridization demonstrated a dramatic reduction (approximately 68%) in the S1 mRNA following isoproterenol injection in proliferation-responsive parotid glands and a mild reduction (approximately 20%) of S1 steady-state messages in the proliferation-refractile submandibular glands [14].
• Moreover, wst/wst thymocytes are more sensitive to apoptosis induced by gamma radiation, heat shock, alpha-CD3 stimulation, and dexamethasone treatment in vitro [15].
• It is possible to fragment the DNA under appropriate conditions by the single-strand-specific nuclease S1 at the site of these A+T-rich zones and to obtain, on alkaline sucrose gradients, a bimodal pattern of DNA fragments of the size corresponding to the pattern observed by electron microscopy [16].
• Here, we report that eEF1A2 directly binds to and activates phosphatidylinositol 4-kinase III beta (PI4KIIIbeta), an enzyme that converts phosphatidylinositol to phosphatidylinositol 4-phosphate [17].
• A morphometric analysis of motor neurons in the spinal cord was performed on 2-hydroxyethyl methacrylate-embedded tissue from ten wst/wst mice, ten littermates (wst/+, +/+) without clinical deficits, and ten parental (+/+) control mice [18].

Regulatory relationships of Eef1a2

• In this article, we report that the expression of eEF1A-2/S1 protein is activated upon myogenic differentiation [12].

Other interactions of Eef1a2

• We have focused on the protein with the highest frequency of hits, peroxiredoxin I (Prdx-I), for in-depth study of its functional implication for eEF1A-2 [10].
• Mice that are homozygous for the recessive mutation wasted (wst) appear normal until soon after weaning, but then develop tremors and ataxia, undergo atrophy of the thymus and spleen, and die by around 28 days of age [19].
• Lymphoproliferative responsiveness to Con A was markedly altered in the wst/wst thymus and spleen, in an age-dependent fashion, compared with normal littermates [4].
• Northern analysis and RNase protection assays have revealed that S1 mRNA is present only in brain, heart, and muscle, while EF-1 alpha mRNA has been detected in all tissues surveyed so far [20].
• Homozygous wabbler-lethal (wl) and wasted (wst) showed hyposensitivity which for the latter may be connected with enhanced cell killing [21].

Analytical, diagnostic and therapeutic context of Eef1a2

• Linkage mapping around the ragged (Ra) and wasted (wst) loci on distal mouse chromosome 2 [19].
• We sequenced the 5' end of one genomic clone and determined the length of the cloned fragment that was protected by eEF-Tu mRNA in S1 nuclease protection assays [2].
• Northern blot analysis shows that the S1 message is most abundant in G0 phase of 3T3 mouse fibroblasts, but becomes significantly reduced in G1 and S phase cells [22].
• Primary sequence analyses indicate that the derived amino acid sequence of S1 shares high homology (greater than 92.6%) with human elongation factor 1 alpha (EF-1 alpha), whereas the 5'- and 3'-untranslated regions are less than 20% homologous [22].
• Thoracic/abdominal muscles from wst/wst mice aged 17 days showed evidence of progressive denervation of motor endplates, including weak synaptic transmission and retraction of motor nerve terminals [5].

References