Eukaryotic translation initiation factor 4F complex (eIF4F complex) (eIF4F)

The eukaryotic translation initiation factor 4F (eIF4F) complex is a heterotrimeric protein assembly consisting of eIF4E (cap-binding protein), eIF4A (RNA helicase), and eIF4G (scaffold protein). It serves as a central integration point for oncogenic signaling pathways, such as PI3K/AKT/mTOR and MAPK, which hyperactivate the complex to drive tumor progression [1][2]. The eIF4F complex is responsible for the selective translation of a subset of pathological mRNAs that encode critical oncoproteins and regulators of tumor biology, including c-Myc, Cyclin D1, and VEGF [1][3]. These mRNAs typically possess long, structured 5' untranslated regions (UTRs) that make their translation highly dependent on eIF4F activity compared to housekeeping mRNAs [2]. Therapeutic strategies targeting this complex, such as selective translation regulation inhibitors (STRIs), aim to downregulate multiple oncogenic drivers simultaneously by blocking the translation of these specific mRNA transcripts [1][4]. Clinical-stage drugs like zotatifin and tomivosertib target components of this complex or its upstream activating kinases to restore normal translational control in cancer cells [1].

Other names

eIF4FeIF4F initiation complexmRNA cap-binding complexSelective translation regulation target

Inhibition of the translation initiation complex to selectively prevent the synthesis of oncoproteins from mRNAs with complex 5' UTRs.