Control of the eIF4E activity: structural insights and pharmacological implications.
4E-binding proteins (4E-BPs)
Canonical eIF4E-binding motif
Non-canonical eIF4E-binding motif
Therapeutic target
Translation initiation
eIF4E
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
09
03
2021
accepted:
08
09
2021
revised:
28
08
2021
pubmed:
21
9
2021
medline:
9
11
2021
entrez:
20
9
2021
Statut:
ppublish
Résumé
The central role of eukaryotic translation initiation factor 4E (eIF4E) in controlling mRNA translation has been clearly assessed in the last decades. eIF4E function is essential for numerous physiological processes, such as protein synthesis, cellular growth and differentiation; dysregulation of its activity has been linked to ageing, cancer onset and progression and neurodevelopmental disorders, such as autism spectrum disorder (ASD) and Fragile X Syndrome (FXS). The interaction between eIF4E and the eukaryotic initiation factor 4G (eIF4G) is crucial for the assembly of the translational machinery, the initial step of mRNA translation. A well-characterized group of proteins, named 4E-binding proteins (4E-BPs), inhibits the eIF4E-eIF4G interaction by competing for the same binding site on the eIF4E surface. 4E-BPs and eIF4G share a single canonical motif for the interaction with a conserved hydrophobic patch of eIF4E. However, a second non-canonical and not conserved binding motif was recently detected for eIF4G and several 4E-BPs. Here, we review the structural features of the interaction between eIF4E and its molecular partners eIF4G and 4E-BPs, focusing on the implications of the recent structural and biochemical evidence for the development of new therapeutic strategies. The design of novel eIF4E-targeting molecules that inhibit translation might provide new avenues for the treatment of several conditions.
Identifiants
pubmed: 34541613
doi: 10.1007/s00018-021-03938-z
pii: 10.1007/s00018-021-03938-z
pmc: PMC8558276
doi:
Substances chimiques
Eukaryotic Initiation Factor-4E
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
6869-6885Informations de copyright
© 2021. The Author(s).
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