Role of Eukaryotic Initiation Factors during Cellular Stress and Cancer Progression

Figure 1

An overview of eukaryotic translation initiation. Most eukaryotic mRNAs contain a 5′m⁷G cap which is bound by eukaryotic initiation factor 4F complex (eIF4E, eIF4G, and eIF4A). The 43S preinitiation ribosome complex which contains ternary complex (Tc) (eIF2-GTP-initiator tRNA) is recruited to the 5′ end of mRNAs via eIF3-eIF4G interaction. With the help of eIF4A (RNA helicase) the preinitiation complex is thought to scan mRNA until the start codon (AUG) is found. Subsequently, the 48S initiation complex is formed and Tc delivers tRNA into the P-site of the ribosome. Then, eIF5 binds to the 48S initiation complex and induces GTPase activity of eIF2α. Upon GTP hydrolysis, all protein factors are released from the 40S ribosome subunit. Subsequently, eIF2α is recharged with GTP by “GDP to GTP” exchange factor eIF2B. Finally, eIF5B unites the 60S and 40S ribosome subunits to form the 80S initiation complex and translation elongation commences.