Apoptosis Rate Can Be Accelerated or Decelerated by Overexpression or Reduction of the Level of Elongation Factor-1α

doi:10.1006/excr.1997.3819

Experimental Cell Research

Volume 238, Issue 1, 10 January 1998, Pages 168-176

https://doi.org/10.1006/excr.1997.3819 Get rights and content

Abstract

Peptide chain elongation factor-1α (EF-1α) is required for the binding of aminoacyl-tRNAs to acceptor sites of ribosomes during protein synthesis. More recently, EF-1α 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-1α is regulated in many situations such as growth arrest, transformation, and aging. Because of this regulation of EF-1α in various states of cell life, and its key position in protein synthesis as well as cytoskeletal organization, we chose to investigate the effect of its expression levels on 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-1α on apoptosis is of particular interest since it may affect both protein synthesis and cytoskeletal organization. For example, reduction of EF-1α leads to a reduced protein synthesis rate, which might reduce the presence of those “killer factors” triggering apoptosis. EF-1α involvement in cytoskeletal organization is another example, since cytoskeletal organization undergoes dramatic changes during apoptosis. Thus, this study has been planned to ascertain whether hypo- and hyperexpression of EF-1α protein, achieved by constructing expression vectors with the EF-1α 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-1α provides cells significant protection from apoptotic cell death and (2) EF-1α overexpression causes a faster rate of cell death. These findings suggest that when EF-1α 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-1α may be one of the global pivotal regulators modulating the rate of apoptosis.

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Citation Excerpt :
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^☆: HolbrookMartinLochsin

¹: To whom correspondence and reprint requests should be addressed at Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755, Chemin de la Côte Ste.-Catherine, Montréal, Québec, Canada H3T 1E2. Fax: (514) 340-8295.

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Regular ArticleApoptosis Rate Can Be Accelerated or Decelerated by Overexpression or Reduction of the Level of Elongation Factor-1α☆

Abstract

Trends Biochem. Sci.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Exp. Cell Res.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Genes Dev.

EMBO J.

Microbiol. Rev.

Cellular Aging and Cell Death

EMBO J.

Regular Article
Apoptosis Rate Can Be Accelerated or Decelerated by Overexpression or Reduction of the Level of Elongation Factor-1α☆