Eukaryotic translation initiation factor 4E (eIF4E):Eukaryotic translation initiation factor 4G (eIF4G) interaction (eIF4E:eIF4G)

The eIF4E:eIF4G interaction is the rate-limiting step in the initiation of eukaryotic cap-dependent translation [3, 11]. eIF4E binds to the 5' 7-methylguanosine cap of mRNA, while eIF4G acts as a scaffold to recruit the eIF4A helicase and the 43S pre-initiation complex [3, 14]. This interaction is essential for the assembly of the eIF4F complex, which is frequently overactive in various malignancies [4, 11]. In cancer, elevated eIF4E levels lead to the disproportionate translation of weak mRNAs encoding oncogenic proteins like c-MYC and Cyclin D1 [2, 4]. Small molecule inhibitors like 4EGI-1 and 4E1RCat have been developed to disrupt this protein-protein interaction, effectively mimicking the natural inhibitory function of 4E-binding proteins (4E-BPs) [2, 7]. Beyond oncology, targeting this interaction shows potential in treating viral infections, such as those caused by coronaviruses, which rely on the host's translation machinery [5]. It is also being investigated for neurodevelopmental disorders like Fragile X syndrome, where dysregulated translation initiation contributes to synaptic defects [22]. Therapeutic challenges include achieving high specificity for the eIF4E:eIF4G interface and overcoming the poor drug-like properties of early-generation inhibitors [6, 21].

Other names

eIF4E-eIF4G interactioneIF4F complex formationeIF4E/eIF4G associationeIF4E-eIF4G protein-protein interaction

Inhibition of the protein-protein interaction between eIF4E and eIF4G to prevent the assembly of the eIF4F translation initiation complex, thereby blocking cap-dependent translation.