title: Control of oncogenesis by eIF2α phosphorylation: implications in PTEN and PI3K-Akt signaling and tumor treatment.
abstract: 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.
authors.affiliation: Lady Davis Institute, McGill University, Montreal, QC, H3T 1E2, Canada.
authors.forename: Antonis E
authors.initials: AE
authors.lastname: Koromilas
authors.forename: Zineb
authors.initials: Z
authors.lastname: Mounir
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015852:Eukaryotic Initiation Factor-2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human