Phospho-eIF2alpha (Ser51) Blocking Peptide

Phosphorylation of the eukaryotic initiation factor 2 (eIF2) α subunit is a well-documented mechanism to downregulate protein synthesis under a variety of stress conditions. eIF2 binds GTP and Met-tRNAi and transfers Met-tRNA to the 40S subunit to form the 43S preinitiation complex (1,2). eIF2 promotes a new round of translation initiation by exchanging GDP for GTP, a reaction catalyzed by eIF2B (1,2). Kinases that are activated by viral infection (PKR), endoplasmic reticulum stress (PERK/PEK), amino acid deprivation (GCN2), or heme deficiency (HRI) can phosphorylate the α subunit of eIF2 (3,4). This phosphorylation stabilizes the eIF2-GDP-eIF2B complex and inhibits the turnover of eIF2B. Induction of PKR by IFN-γ and TNF-α induces potent phosphorylation of eIF2α at Ser51 (5,6). 1.Kimball, S.R. (1999) Int. J. Biochem. Cell Biol. 31, 25-29. 2.de Haro, C. et al. (1996) FASEB J. 10, 1378-87. 3.Kaufman, R.J. (1999) Genes Dev. 13, 1211-33. 4.Sheikh, M.S. and Fornace Jr., A.J. (1999) Oncogene 18, 6121-8. 5.Cheshire, J.L. et al. (1999) J. Biol. Chem. 274, 4801-6. 6.Zamanian-Daryoush, M. et al. (2000) Mol. Cell. Biol. 20, 1278-90.