eIF4B

eIF4B, or eukaryotic initiation factor 4B, is a conserved cytoplasmic protein that promotes cap-dependent translation initiation in eukaryotic cells. It functions as a cofactor in the initiation process, working alongside the eIF4F complex (consisting of eIF4E, eIF4G, and the RNA helicase eIF4A) to enhance recruitment of the ribosome to mRNA.

The primary role of eIF4B is to stimulate the RNA helicase activity of eIF4A. By binding RNA and interacting with eIF4A, eIF4B increases ATPase activity and facilitates unwinding of secondary structures in the 5' untranslated region of mRNAs. This activity helps the 43S pre-initiation complex scan the mRNA more efficiently and promotes accurate start codon recognition, especially for mRNAs with highly structured 5' UTRs.

eIF4B interacts with multiple components of the initiation machinery, including eIF4A and other initiation factors such as eIF3, and it functions within the broader context of the translation initiation complex. Its activity is regulated by signaling pathways that respond to nutrients and growth cues; in mammals, eIF4B is a substrate of S6 kinase 1 (S6K1), a downstream effector of the mTOR pathway. Phosphorylation of eIF4B enhances its ability to stimulate eIF4A and translation.

Biological significance of eIF4B lies in its contribution to efficient protein synthesis and cell growth. It is particularly important for the translation of mRNAs with structured 5' UTRs, and its dysregulation can influence cellular proliferation and stress responses. Alterations in translation initiation factors, including eIF4B, have been associated with various diseases, notably cancer, where control of protein synthesis is often perturbed.