Eukaryotic translation initiation factor 4F complex (eIF4F)

The **Eukaryotic translation initiation factor 4F complex (eIF4F)** is a heterotrimeric protein complex essential for initiating cap-dependent translation in eukaryotic cells[2][3][5]. It comprises three primary subunits: **eIF4E** (cap-binding protein), **eIF4A** (DEAD-box RNA helicase), and **eIF4G** (scaffold protein)[2][5]. eIF4F binds the 5' cap structure of messenger RNAs and recruits the small ribosomal subunit, facilitating translation initiation[2][4]. It functions as a critical node in multiple oncogenic signaling pathways—including Ras, Myc, and PI3K-TOR—and is required for efficient translation of mRNAs with structured 5′ UTRs, which often encode growth-promoting and survival proteins[1][5]. Aberrant regulation or amplification of eIF4F components, particularly eIF4E and eIF4G, is implicated in various cancers, driving malignant progression, transformation, and therapeutic resistance[1][3]. The complex is a validated therapeutic target, and several natural product inhibitors selectively block its activity, mainly by targeting its helicase subunit, eIF4A[2]. However, systemic inhibition presents safety concerns, as eIF4F also mediates general protein synthesis critical to normal cellular function[1][5].

Other names

Eukaryotic initiation factor 4F complexeIF4Ftranslation initiation factor eIF4F

Inhibition of eIF4A helicase activity (e.g., rocaglamide A, hippuristanol, pateamine A) - Disruption of eIF4E-cap binding (experimental)