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

The protein-protein interaction between Eukaryotic translation initiation factor 4E (eIF4E) and Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) is a fundamental regulatory switch in the control of cap-dependent translation initiation (UniProt P06730, P60866). eIF4E is the rate-limiting component of the eIF4F complex, responsible for binding the 5' cap of mRNAs and recruiting the ribosome to initiate protein synthesis. 4E-BP1 acts as a translational repressor by binding to eIF4E at the same site as the scaffold protein eIF4G, thereby sequestering eIF4E and preventing the assembly of the active translation machinery (NIH, PMC230746). This interaction is dynamically regulated by the mTORC1 signaling pathway; when 4E-BP1 is phosphorylated by mTORC1, it loses its affinity for eIF4E, releasing the factor to promote protein synthesis (Wikipedia, 4E-BP1). In many human cancers, the eIF4E:4E-BP1 axis is severely dysregulated, often through the hyperphosphorylation of 4E-BP1, which leads to the constitutive activation of eIF4E and the selective translation of oncogenic proteins involved in cell survival and proliferation (Cancer Res. 2007, 67:7551). Therapeutic interventions aim to either stabilize the eIF4E:4E-BP1 complex using mTOR inhibitors or employ small-molecule inhibitors like 4EGI-1 that mimic 4E-BP1 to disrupt the eIF4E:eIF4G interaction (Cell 2007, 128:257).

Other names

eIF4E/4E-BP1 complexeIF4E-4EBP1 interaction4E-BP1:eIF4E axisPHAS-I:eIF4E interaction

Inhibition of the eIF4E:eIF4G interaction by either stabilizing the eIF4E:4E-BP1 complex (via mTORC1 inhibition) to sequester eIF4E, or by using small-molecule inhibitors that mimic 4E-BP1 to competitively block the eIF4G binding site on eIF4E.