Control of oncogenesis by eIF2α phosphorylation: implications in PTEN and PI3K-Akt signaling and tumor treatment

Future Oncol. 2013 Jul;9(7):1005-15. doi: 10.2217/fon.13.49.


mRNA translation plays an important role in tumor development and represents a valid target of pharmaceutical intervention in cancer. A key step in mRNA translation involves the regulation of initiation by the eukaryotic initiation factor eIF2. Eukaryotic cells respond to various forms of stress by inducing the phosphorylation of the α-subunit of eIF2 at S51, a modification that leads to protein synthesis inhibition. Phosphorylated eIF2α can act either as a promoter of cell survival or an inducer of cell death in response to distinct stimuli. Increased eIF2α phosphorylation has a cytoprotective function in response to genetic or pharmacological inhibition of the PI3K-Akt pathway but also exhibits a proapoptotic function downstream of the PTEN tumor suppressor, independent of PI3K-Akt signaling inhibition. The functional interplay between the PI3K-Akt and eIF2α phosphorylation pathways may have important implications in the design of anti-tumor therapies that depend on the cell fate decisions of phosphorylated eIF2α.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Cell Survival
  • Eukaryotic Initiation Factor-2 / metabolism*
  • Humans
  • Mice
  • Molecular Targeted Therapy*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction


  • Eukaryotic Initiation Factor-2
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human