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

Cell Death Differ. 2002 Aug;9(8):856-61. doi: 10.1038/sj.cdd.4401078.

Abstract

To identify genes that contribute to apoptotic resistance, IL-3 dependent hematopoietic cells were transfected with a cDNA expression library and subjected to growth factor withdrawal. Transfected cells were enriched for survivors over two successive rounds of IL-3 withdrawal and reconstitution, resulting in the identification of a full-length elongation factor 1 alpha (EF-1alpha) cDNA. Ectopic EF-1alpha expression conferred protection from growth factor withdrawal and agents that induce endoplasmic reticulum stress, but not from nuclear damage or death receptor signaling. Overexpression of EF-1alpha did not lead to growth factor independent cell proliferation or global alterations in protein levels or rates of synthesis. These findings suggest that overexpression of EF-1alpha results in selective resistance to apoptosis induced by growth factor withdrawal and ER stress.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Division / drug effects
  • Cell Division / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Eukaryotic Cells / drug effects
  • Eukaryotic Cells / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Humans
  • Interleukin-3 / deficiency*
  • Interleukin-3 / pharmacology
  • Peptide Elongation Factor 1 / genetics
  • Peptide Elongation Factor 1 / metabolism*
  • Protein Synthesis Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stress, Physiological / genetics
  • Stress, Physiological / metabolism*
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • Enzyme Inhibitors
  • Interleukin-3
  • Peptide Elongation Factor 1
  • Protein Synthesis Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein