Eukaryotic translation initiation factor 4E (eIF4E) (eIF4E)

Eukaryotic translation initiation factor 4E (eIF4E) is the principal cap-binding protein required for the initiation of cap-dependent mRNA translation in eukaryotic cells. eIF4E binds to the 7-methylguanosine (m7G) cap structure at the 5' end of mRNAs, recruiting them to the ribosome through the eIF4F complex (which also includes eIF4G and eIF4A). Regulation of eIF4E activity occurs via interactions with 4E-binding proteins (4EBPs), eIF4G, and post-translational modifications, particularly phosphorylation at Ser209 by MNK1/2 kinases downstream of the MAPK/ERK pathway. eIF4E activity is tightly linked to cell growth, oncogenic transformation, and plasticity; its overexpression or hyperphosphorylation promotes translation of mRNAs involved in proliferation and survival, contributing to carcinogenesis and tumor progression. Resulting dysregulation is seen in a variety of cancers and neurodevelopmental diseases, making eIF4E and its phosphorylation pathway attractive therapeutic targets.

Other names

EIF4EEukaryotic translation initiation factor 4EeIF4E1Cap-binding proteinmRNA cap-binding protein eIF4E

Inhibiting eIF4E-cap binding (direct or allosteric inhibitors); Disrupting eIF4E/eIF4G interaction (e.g., competitive inhibitors like 4EGI-1); Preventing eIF4E phosphorylation (targeting upstream kinases such as MNK1/2); Upregulating 4E-BPs to sequester eIF4E and prevent translation initiation