Elongation factor-1α gene determines susceptibility to transformation

Abstract

Elongation factor-1 alpha (EF-1 alpha), an essential component of the eukaryotic translational apparatus, is a GTP-binding protein that catalyses the binding of aminoacyl-transfer RNAs to the ribosome. Expression of the EF-1 alpha gene decreases towards the end of the lifespans of mouse and human fibroblasts, but forced expression of EF-1 alpha prolongs the lifespan of Drosophila melanogaster. Eukaryotic initiation factor-4E, another component of the translational machinery, is mitogenic or oncogenic when constitutively expressed in some mammalian cells. Thus, components of the protein synthesis apparatus seem to be involved in the control of cell proliferation. Using expression cloning, we have isolated a complementary DNA clone from a BALB/c 3T3 mouse fibroblast variant, A31-I-13 (ref. 10), which specifies a factor determining the susceptibility of BALB/c3T3 to chemically and physically induced transformation. Here we report that the factor is EF-1 alpha and that its constitutive expression causes BALB/c 3T3 A31-I-1 (ref. 10), C3H10T1/2 (ref. 11) and Syrian hamster SHOK fibroblasts to become highly susceptible to transformation induced by 3-methylcholanthrene and ultraviolet light. EF-1 alpha messenger RNA is also constitutively expressed in a quiescent culture of the highly susceptible variant A31-I-13. We conclude that the removal of regulation of the expression of these components of the translational machinery may predispose cells to become more susceptible to malignant transformation.

Elongation factor-1 alpha is a selective regulator of growth factor withdrawal and ER stress-induced apoptosis

“…Previous findings suggest that the constitutive expression of EF-1a can sensitize cultured cells to transformation by chemical agents or irradiation, but is not itself transforming. 17 The results reported here provide a molecular explanation for these earlier observations. EF-1a may create an environment suitable for mutagens to induce transformation by increasing cellular resistance to apoptosis as has been proposed for Bcl-2 and Bcl-x L .…”

“…17 We therefore investigated whether the protection observed in FL5.12 cells was a consequence of IL-3-independent proliferation. Cells were incubated with the nucleotide analog BrdU, and the BrdU incorporated into newly synthesized DNA was used to determine the percentage of cycling cells in the population.…”

Antisense inhibition of the PTI-1 oncogene reverses cancer phenotypes

“…Overexpression of the eukaryotic protein synthesis initiation factor eIF-4E can profoundly affect cellular physiology; effects include cooperating with viral oncogenes (such as v-myc and adenovirus E1A) to transform primary rodent cells (30), eliciting a tumorigenic phenotype in established rodent cells (31), and cooperating with MAX to produce a tumorigenic and metastatic phenotype in Chinese hamster ovary (CHO) cells (32). Elevated expression of EF-1␣, which normally functions to ensure proper codon-anticodon binding interactions at the A site of the ribosome (28,29), also modifies cellular properties, rendering both mouse and Syrian hamster cells susceptible to carcinogen-and ultraviolet light-induced transformation (33). Enhanced levels of EF-1␣ are also found in tumors of the pancreas, colon, breast, lung, and stomach relative to adjacent normal tissue (34).…”

A Higher Plant Extracellular Vitronectin-Like Adhesion Protein Is Related to the Translational Elongation Factor-1a

“…Besides its role in the elongation phase of protein synthesis, EF-la has been found to be an actin binding protein (Yang et al, 1990), an activator for the carrot phosphatidylinositol-4-kinase (Yang et al, 1993), and a malignant transformation determinant in animal cell cultures (Tatsuka et al, 1992). Our study illustrates that proteins structurally related to EF-1 a may function in the ECM by possibly interacting with membrane receptor proteins.…”