The Human Elongation Factor 1 A-2 Gene (EEF1A2): Complete Sequence and Characterization of Gene Structure and Promoter Activity

Bischoff, Claus; Kahns, Søren; Lund, Ann; Jørgensen, Helle F.; Præstegaard, Morten; Clark, Brian F. C.; Leffers, Henrik

doi:10.1006/geno.2000.6271

Cited by 21 publications

(16 citation statements)

References 37 publications

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“…The promoter region of eEF1A2 contains 12 E-boxes, 3 Egr family of proteins, 1 GATA motif, and 1 MEF2 binding site (48). However, insulin or serum stimulation of PA-1 cells failed to induce the DNA binding of Egr1 and MEF1 (data not shown).…”

Section: Discussionmentioning

confidence: 89%

Resveratrol Suppresses Growth of Human Ovarian Cancer Cells in Culture and in a Murine Xenograft Model: Eukaryotic Elongation Factor 1A2 as a Potential Target

Lee¹,

Choi²,

Kundu³

et al. 2009

Cancer Research

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The eukaryotic elongation factor 1A2 (eEF1A2) is known to retain oncogenic potential and is recognized as a novel target for cancer prevention and therapy. Resveratrol (trans-3,4 ¶,5-trihydroxystilbene), a phytoalexin present in grapes, has been reported to possess chemopreventive and chemotherapeutic activities. In the present study, we examined the growth-inhibitory effects of resveratrol in human ovarian cancer PA-1 cells, considering eEF1A2 as a potential molecular target. Pretreatment with resveratrol attenuated proliferation of serum-starved PA-1 cells stimulated with insulin or serum. Resveratrol also activated caspase-9, -7, and -3 and induced apoptosis in PA-1 cells in the presence of insulin or serum. Insulin or serum stimulation of PA-1 cells resulted in the marked induction of eEF1A2, which was suppressed by pretreatment with resveratrol. Moreover, resveratrol inhibited insulin-or serum-induced soft-agar colony formation in eEF1A2-transfected NIH3T3 cells. An antibody array directed to assess the phosphorylation of protein kinases revealed that treatment with insulin or serum induced the phosphorylation of Akt in PA-1 cells. Pharmacologic inhibition of Akt with LY294002 abrogated insulin-or serum-induced eEF1A2 expression and increased the caspase-3 activity. In another experiment, i.p. administration of resveratrol retarded the growth of PA-1 cell xenograft and the expression of eEF1A2 in athymic nude mice in association with decreased bromodeoxyuridine positivity, reduced expression of proliferating cell nuclear antigen, increased the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and caspase-3 staining, and diminished CD31 positivity. Taken together, eEF1A2 may be considered as a potential molecular target for the antiproliferative effects of resveratrol in PA-1 ovarian cancer cells.

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Section: Discussionmentioning

confidence: 89%

Resveratrol Suppresses Growth of Human Ovarian Cancer Cells in Culture and in a Murine Xenograft Model: Eukaryotic Elongation Factor 1A2 as a Potential Target

Lee¹,

Choi²,

Kundu³

et al. 2009

Cancer Research

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“…In comparison, eEF1A-2 was synthesized efficiently even in the absence of growth factors. Because eEF1A-2 mRNA does not contain a TOP element in its 5Ј-UTR (12,44), the abundance of eEF1A-2 in PC12 cells is consistent with its status as a non-TOP mRNA, such as ␤-actin, that is primarily polyribosome-associated (4). However, at this time we cannot explain the presence of eEF1A-2 in non-differentiated PC12 cells because its expression in neurons is terminal differentiation-dependent (10).…”

Section: Discussionmentioning

confidence: 99%

Nerve Growth Factor Specifically Stimulates Translation of Eukaryotic Elongation Factor 1A-1 (eEF1A-1) mRNA by Recruitment to Polyribosomes in PC12 Cells

Petroulakis¹,

Wang²

2002

Journal of Biological Chemistry

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During postnatal brain development the level of peptide elongation factor-1A (eEF1A-1) expression declines and that of the highly homologous isoform, eEF1A-2, increases in neurons. eEF1A-1 is implicated in cytoskeletal interactions, tumorigenesis, differentiation, and the absence of eEF1A-2 is implicated in neurodegeneration in the mouse mutant, wasted. The translation of eEF1A-1 mRNA is up-regulated via mitogenic stimulation. However, it is not known if eEF1A-1 mRNA translation is regulated by neurotrophins or if its synthesis is differentially regulated than that of the neuronal isoform, eEF1A-2. Regulated translation of these factors by neurotrophins, particularly by the Trk class of neurotrophin receptors, would implicate them in differentiation, survival, and neuronal plasticity. In this study, we investigated the effect of nerve growth factor (NGF) stimulation on the synthesis of eEF1A-1 and eEF1A-2. We found that NGF stimulation causes a preferential synthesis of eEF1A-1 over eEF1A-2 in PC12 cells. We analyzed the co-sedimentation of eEF1A-1 mRNA with polyribosome fractions in sucrose gradients, and found that NGF stimulation enriched the presence of eEF1A-1 mRNA in polyribosomes, indicating that the translation of eEF1A-1 mRNA is regulated by NGF. Inhibitors of phosphatidylinositol 3-kinase (LY 294002), mammalian target of rapamycin (rapamycin), and the NGF receptor, TrkA (K-252a), but not of mitogenactivated protein kinase (PD 98059), prevented the recruitment of eEF1A-1 mRNA to polyribosomes. The mobilization of eEF1A-1 mRNA to polyribosomes was rapamycin-sensitive in both proliferating and differentiated PC12 cells, indicating the importance of this pathway during differentiation. Our data shows that after growth factor withdrawal, an NGF-signaling pathway stimulates eEF1A-1 mRNA translation in proliferating and differentiated PC12 cells. Therefore, eEF1A-1 mRNA is a specific translational target of TrkA signaling.

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“…[60][61][62] These findings suggest that eEF1A2 expression may be controlled by ZNF217, which is an upstream transcription factor, although there is the possibility of involvement of other transcription factors, such as the EGR (early growth response) family and MEF2 (myocyte enhancer factor 2) that have consensus sequences for binding at the promoter region of EEF1A2. 63 Further investigation is necessary to determine the precise role for eEF1A2 in controlling the development of specific cancers.…”

Section: Oncogenic Potential Of Ef1a2mentioning

confidence: 99%

eEF1A2 as a Putative Oncogene

Lee

Surh

2009

Annals of the New York Academy of Sciences

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The first evidence for the role of the protein elongation factor eEF1A2 in tumorigenesis was reported by Anand and colleagues who demonstrated that eEF1A2 is overexpressed in about 30% of ovarian tumors and some established ovarian cancer cells. This abnormal expression correlates with a poor prognosis. Since this discovery, there have been several reports suggesting eEF1A2 as a diagnostic marker in various cancers. This review highlights the oncogenic potential of eEF1A2.

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The Human Elongation Factor 1 A-2 Gene (EEF1A2): Complete Sequence and Characterization of Gene Structure and Promoter Activity

Cited by 21 publications

References 37 publications

Resveratrol Suppresses Growth of Human Ovarian Cancer Cells in Culture and in a Murine Xenograft Model: Eukaryotic Elongation Factor 1A2 as a Potential Target

Resveratrol Suppresses Growth of Human Ovarian Cancer Cells in Culture and in a Murine Xenograft Model: Eukaryotic Elongation Factor 1A2 as a Potential Target

Nerve Growth Factor Specifically Stimulates Translation of Eukaryotic Elongation Factor 1A-1 (eEF1A-1) mRNA by Recruitment to Polyribosomes in PC12 Cells

eEF1A2 as a Putative Oncogene

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