Eukaryotic translation initiation factor 3 (eIF3) (eIF3)

Eukaryotic translation initiation factor 3 (eIF3) is the largest and most complex of the initiation factors, consisting of 13 non-identical subunits (eIF3a–m) in mammals [1, 6]. It serves as a central scaffold for the assembly of the 43S pre-initiation complex, facilitating the recruitment of mRNA and the scanning process to identify the start codon [4, 6]. Beyond its core role in initiation, eIF3 is involved in translation termination, ribosomal recycling, and specialized mechanisms like reinitiation and nonsense-mediated decay [4, 13]. In human disease, eIF3 is frequently dysregulated; several subunits, such as eIF3a, eIF3b, and eIF3h, are overexpressed in various cancers and act as proto-oncogenes, while others like eIF3e and eIF3f may function as tumor suppressors [1, 5, 9]. Additionally, eIF3 is often hijacked by viruses, such as the Hepatitis C virus and HIV, to facilitate cap-independent translation via internal ribosome entry sites (IRES) [1, 6]. Because of its pivotal role in protein synthesis and its frequent aberration in malignancies, eIF3 has emerged as a promising therapeutic target [7, 11, 15]. Small molecules like rocaglates and pateamine A have been shown to disrupt eIF3 interactions, and experimental strategies including RNA interference and subunit-specific inhibitors are currently under investigation to modulate its activity in cancer and infectious diseases [8, 12, 18]. The complex also integrates signals from major pathways like mTOR and S6K1, making it a critical node for cellular growth control [6, 9]. Targeting eIF3 offers a strategy to selectively inhibit the translation of oncogenic mRNAs that are highly dependent on its function [16, 19].

Other names

eIF-3Eukaryotic initiation factor 3Eukaryotic translation initiation factor 3 complex

Inhibition of translation initiation by disrupting the assembly of the eIF3 complex or its interaction with other initiation factors and the ribosome [8, 12, 15].