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. Author manuscript; available in PMC: 2016 Jan 18.
Published in final edited form as: Pigment Cell Melanoma Res. 2015 Sep;28(5):501–519. doi: 10.1111/pcmr.12391

Figure 2. mRNA translational regulation.

Figure 2

(A) GTP from the ternary complex of initiator met-tRNA, eIF2, and GTP is hydrolyzed into GDP during translation initiation. GEF activity of eIF2B typically exchanges GDP with GTP to continue translation. However, the α subunit of eIF2 can be phosphorylated by kinases activated by various stresses, such as amino acid starvation, ER stress, heme depletion, and viral infection. The phosphorylation causes a tighter binding of eIF2 to eIF2B, inhibiting GEF activity and thus translation initiation. GADD34 and CReP counter the kinase activity by bringing phosphorylated eIF2α to PP1 for dephosphorylation to enhance translation. (B) The eIF4F complex is regulated by MAPK and PI3K/AKT/mTOR pathways. MAPK activity through MNK1/2 phosphorylates eIF4E and eIF4B, enhancing translation. mTOR phosphorylates 4EBP and p70S6K (S6K) to promote translation.