Comparison models summarizing how eIF4E is not only downstream of the PI3K–AKT pathway (left) but can modulate this PI3K–Akt axis through NBS1 (right). Furthermore, several downstream effectors of Akt (e.g., cyclin A2, B1, D1, and E, Mdm2, and c-Myc) are also targets for eIF4E regulation at the mRNA export level, giving rise to a putative feedback loop. For simplicity, arrows indicate downstream effects (such as phosphorylation), but arrows do not necessarily indicate a single-step process. In yellow are some of the known subsets of mRNAs sensitive to eIF4E export activity that are also downstream effectors of Akt. PML's role as an inhibitor of eIF4E is also shown.