Eukaryotic translation initiation factor 4E:Eukaryotic translation initiation factor 4E-binding protein 1 interaction (eIF4E:4E-BP1 interaction)

The eIF4E:4E-BP1 interaction is a fundamental regulatory mechanism for cap-dependent translation initiation in eukaryotic cells (Sonenberg & Hinnebusch, 2009, New England Journal of Medicine). Eukaryotic translation initiation factor 4E (eIF4E) binds the 7-methylguanosine cap of mRNA, while 4E-binding protein 1 (4E-BP1) acts as a repressor by sequestering eIF4E (UniProt P06730, Q13541). When 4E-BP1 is bound to eIF4E, it prevents the formation of the eIF4F initiation complex, effectively halting the translation of specific mRNAs (Moerke et al., 2007, Cell). This interaction is controlled by the mTORC1 signaling pathway, which phosphorylates 4E-BP1 to trigger its release from eIF4E, thereby activating translation (Bhat et al., 2015, Nature Reviews Drug Discovery). Dysregulation of this axis, often through eIF4E overexpression or 4E-BP1 hyperphosphorylation, is a hallmark of many malignancies and promotes the translation of pro-tumorigenic factors (Silvera et al., 2010, Nature Reviews Cancer). Consequently, the eIF4E:4E-BP1 interface has emerged as a high-priority therapeutic target for cancer treatment. Small molecule inhibitors like 4EGI-1 have been developed to mimic the binding of 4E-BP1 to eIF4E, thereby blocking the oncogenic eIF4E:eIF4G interaction (Moerke et al., 2007, Cell). Other approaches include antisense oligonucleotides and PROTACs designed to reduce eIF4E levels or stabilize the inactive eIF4E:4E-BP1 complex (Graff et al., 2007, Cancer Research).

Other names

eIF4E/4E-BP1 complexeIF4E-4EBP1 interactioneIF4E:EIF4EBP1 interaction4E-BP1:eIF4E interaction

Inhibition of the eIF4E:eIF4G interaction by mimicking 4E-BP1 binding; stabilization of the 4E-BP1:eIF4E complex; competitive inhibition of the eIF4E cap-binding site.