Fig. 1.

Translational control mechanisms. Signaling pathways upstream of translation can be stimulated by activation of several membrane receptors. The activation of these receptors leads to subsequent stimulation of (A) RAS/RAF/ERK pathway and the phosphorylation of eIF4E, and (B) the activation of PI3K/AKT/mTORC1 pathway. mTORC1 phosphorylates and inhibits the translational repressor 4E-BP, resulting in increased eIF4F complex formation, which promotes the recruitment of the ribosome to the cap structure at the 5′ end of the mRNA. This mechanism controls translation of a specific subset of mRNAs. (C) Translation is also regulated via eIF2ɑ pathway, which controls both general translation and translation of mRNAs containing uORFs at their 5′ UTR (e.g. ATF4 and CHOP).