Apoptosis rate can be accelerated or decelerated by overexpression or reduction of the level of elongation factor-1α

Peptide chain elongation factos-1 alpha (EF-1 alpha) is required for the binding of aminoacyl-tRNAs to acceptor sites of ribosomes during protein synthesis. More recently, EF-1 alpha has been shown to be involved in cytoskeletal organization. The elongation factor functions in actin bundling and microtubule severing. Moreover, it can activate the phosphatidylinositol-4 kinase whose substrates are involved in regulation of actin polymerization, The expression level of EF-1 alpha is regulated in many situations such as growth arrest, transformation, and aging. Because of this regulation of EF-1 alpha in various skates of call life, and its key position in protein synthesis as well as cytoskeletal organization, we chose to investigate the effect of its expression levels are apoptosis. Apoptosis is a complex event regulated through numerous activators and inhibitors. In some situations, protein synthesis is required for apoptosis to be triggered, Investigation of the Effect of altered levels of elongation factor-1 alpha on apoptosis is of particular interest since it may affect both protein synthesis and cytoskeletal organization. For example, reduction of EF-1 alpha leads to a reduced protein synthesis rate, which might reduce the presence of those "killer factors" triggering apoptosis. EF-1 alpha involvement in cytoskeletal organization is another example, since cytoskeletal organization undergoes dramatic changes during apoptosis, Thus, this study was been planned to ascertain whether hypo- and hyperexpression of EF-1 alpha protein, achieved by constructing expression vectors with the EF-1 alpha cDNA in its antisense or sense orientation under the control of a cytomegalovirus promoter, can produce stable transfectants with either heightened, or reduced responsiveness to apoptosis stimuli, Our results show the following (1) induction of apoptosis by serum deprivation shows that antisense EF-1 alpha provides cells significant protection from apoptotic cell death aad (2) EF-1 alpha overexpression causes a faster rate of cell death, These findings suggest that when EF-1 alpha protein is abundant the cells are proapoptosis, and vice versa in low abundance the cells are in the mode of antiapoptosis. Therefore, changes in levels of EF-1 alpha may be one of the global pivotal regulators modulating the rate of apoptosis. (C) 1998 Academic Press.