Advances in understanding and targeting eIF4E activity
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ICR Authors
Authors
D'Agostino, S
Davies, C
Powers, M
Clarke, PA
Davies, C
Powers, M
Clarke, PA
Document Type
Journal Article
Date
2025-07-09
Date Accepted
2025-06-16
Abstract
<jats:p>Eukaryotic translation initiation factor 4E (eIF4E) has long been recognised as a pivotal regulator of cap-dependent protein synthesis initiation. More recently, eIF4E has emerged as a multifunctional factor proposed to influence various aspects of RNA metabolism, including nuclear export of mRNA to the cytoplasm. Its versatile roles are largely attributed to its ability to bind the methyl-7-guanosine cap (m7G-cap) of mRNAs and participate in critical protein–protein interactions. Deregulated eIF4E expression or activity has been implicated in several diseases, but it is most prominently studied as an oncogene where its activity can drive cancer onset, progression and drug resistance. Consequently, eIF4E is a highly attractive target for the development of novel anti-tumour therapeutics. Recent advancements have provided new insights into the mechanism of action of eIF4E, leveraging fragment-based compound screening and genetically modified cell models to identify and characterise binding sites on this challenging-to-drug protein target. In this review, we summarise the multiple roles of eIF4E and features that underpin its activity in both the cytoplasm and nucleus, and the key findings related to the modulation of its activity and therapeutic potential.</jats:p>
Citation
Biochemical Society Transactions, 2025, 53 (04), pp. 801 - 822
Source Title
Biochemical Society Transactions
Publisher
PORTLAND PRESS LTD
ISSN
0300-5127
eISSN
1470-8752
Collections
Research Team
RNA Bio and Mol Therap