Translational inhibition by eIF-2-phospholipid complex in mammalian cell-free systems.
The polypeptide chain initiation factor 2 (eIF-2) binds phospholipid (PL) and becomes a potent inhibitor of translation in hemin-supplemented reticulocyte lysates [De Haro et al. (1986) Proc. Natl. Acad. Sci. USA 83, 6711-6715]. This binding is independent of calcium ions and seems to be specific for phosphatidylinositol or phosphatidylserine; phosphatidic and arachidonic acids are inactive. Like alpha-subunit-phosphorylated eIF-2, eIF-2.PL traps GEF in a non-dissociable eIF-2.PL.GEF complex whereby GEF is no longer able to recycle. Initiation is inhibited when no free GEF is available. Translational inhibition by eIF-2.PL is rescued by equimolar amounts of eIF-2.GEF. On the basis of this stoichiometry, we have estimated that reticulocyte lysates contain about 60 pmol of GEF/ml (60 nM). eIF-2.PL also inhibits translation in cell-free mouse liver extracts and this inhibition is prevented by reticulocyte eIF-2.GEF suggesting that GEF also functions in liver. However, the eIF-2.PL complex does not affect translation in such non-mammalian eukaryotic systems as wheat germ and Drosophila embryos.
Pelaez
F
F
Centro de Biologia Molecular, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
de Haro
C
C
D000818:Animals; D002474:Cell-Free System; D004330:Drosophila / Q000235:genetics; D015852:Eukaryotic Initiation Factor-2; D008099:Liver / Q000378:metabolism; D051379:Mice; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D013045:Species Specificity; D013379:Substrate Specificity; D014908:Triticum / Q000235:genetics
D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D010743:Phospholipids; D011506:Proteins