eIF4E1B Activators

Eukaryotic translation initiation factor 4E family member 1B (EIF4E1B) activators are a class of compounds that influence the eukaryotic initiation phase of protein synthesis either through direct interaction with EIF4E1B or by modulating the signaling pathways that govern its activity. For instance, the cap analog 7-Methylguanosine 5'-triphosphate directly enhances the activity of EIF4E1B by mimicking the natural mRNA cap, facilitating EIF4E1B's role in the recruitment of ribosomes for translation initiation. Substances like insulin and rapamycin modulate the mTORpathway, which plays a pivotal role in the regulation of EIF4E1B through its interaction with 4E-BP proteins. When insulin activates the PI3K/Akt/mTOR pathway, it leads to the phosphorylation and subsequent release of EIF4E1B from inhibitory 4E-BP proteins, thereby increasing EIF4E1B's availability to initiate translation. Conversely, rapamycin inhibits mTORC1, leading to less phosphorylated 4E-BP and a resultant increase in free EIF4E1B to participate in translation initiation.

Other compounds such as Paclitaxel and LY294002 indirectly influence EIF4E1B activity through their effects on the mTOR signaling pathway. Paclitaxel, by stabilizing microtubules, can activate mTOR and promote EIF4E1B activity. LY294002, though primarily a PI3K inhibitor, can induce compensatory feedback that activates mTORC1, thus enhancing EIF4E1B function. Similarly, U0126 and Triciribine, although they are inhibitors of MEK1/2 and Akt respectively, can trigger feedback loops that ultimately promote mTORC1 signaling and increase EIF4E1B activity. Resveratrol, by activating sirtuins, influences the PI3K/Akt/mTOR axis and can lead to the enhancement of EIF4E1B activity. Metformin, through AMPK activation, inhibits mTORC1 but can lead to reduced phosphorylation of 4E-BPs, thus raising the levels of active EIF4E1B.