Elongation factor-1α gene determines susceptibility to transformation

ELONGATION factor-lα (EF-lα), an essential component of the eukaryotic translational apparatus, is a GTP-binding protein that catalyses the binding of aminoacyl-transfer RNAs to the ribosome 1–3 . Expression of the EF-lα gene decreases towards the end of the lifespans of mouse and human fibroblasts 4,5 , but forced expression of EF-lα prolongs the lifespan of Drosophila melanogaster 6 . Eukaryotic initiation factor-4E, another component of the translational machinery, is mitogenic or oncogenic when constitutively expressed in some mammalian cells 7–9 . 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/c 3T3 to chemically and physically induced transformation. Here we report that the factor is EF-lα and that its constitutive expression causes BALB/c 3T3 A31-I-1 (ref. 10), C3H10T1/2 (ref. 11) and Syrian hamster SHOK 12 fibroblasts to become highly susceptible to transforma-tion induced by 3-methylcholanthrene and ultraviolet light. EF-lα messenger RNA is also constitutively expressed in a quiescent culture of the highly susceptible variant A31-1-13. We conclude that the removal of regulation of the expression of these com-ponents of the translational machinery may predispose cells to become more susceptible to malignant transformation.