ELONGATION FACTOR-1-ALPHA GENE DETERMINES SUSCEPTIBILITY TO TRANSFORMATION

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 ribosome1-3. Expression of the EF-1-alpha gene decreases towards the end of the lifespans of mouse and human fibroblasts4,5, but forced expression of EF-1-alpha prolongs the lifespan of Drosophila melanogaster6. Eukaryotic initiation factor-4E, another component of the translational machinery, is mitogenic or oncogenic when constitutively expressed in some mammalian cells7-9. 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-1-alpha and that its constitutive expression causes BALB/c 3T3 A31-I-1 (ref. 10), C3H10T1/2 (ref. 11) and Syrian hamster SHOK12 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.