EIF4EBP1

Description

The EIF4EBP1 (eukaryotic translation initiation factor 4E binding protein 1) is a protein-coding gene located on chromosome 8.

EIF4EBP1 (eukaryotic translation initiation factor 4E-binding protein 1) is a protein that in humans is encoded by the EIF4EBP1 gene. It inhibits cap-dependent translation by binding to translation initiation factor eIF4E. Phosphorylation of 4E-BP1 results in its release from eIF4E, allowing cap-dependent translation to continue and increasing the rate of protein synthesis. Phosphorylated 4E-BP1 is considered a marker of upstream signaling (mTOR) activation. It has seven phosphorylation sites, with the most crucial being Thr 37/Thr 46, Thr 70, and Ser 65. Phosphorylation of Ser 65 and Thr 70 alone is insufficient to block the inhibition of mRNA translation by 4E-BP1, indicating that multiple phosphorylation events are required to increase protein synthesis rates. This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Its interaction with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals, including UV irradiation and insulin signaling, causing its dissociation from eIF4E and activation of cap-dependent mRNA translation. High levels of phosphorylated 4E-BP1 have been widely observed in human cancers, and are associated with a worse outcome in several malignancies.

EIF4EBP1 acts as a repressor of translation initiation, controlling the activity of EIF4E by hindering its integration into the eIF4F complex. In its hypophosphorylated state, EIF4EBP1 strongly binds to EIF4E and competes with EIF4G1/EIF4G3, suppressing translation. Conversely, in its hyperphosphorylated state, EIF4EBP1 detaches from EIF4E, enabling the interaction of EIF4G1/EIF4G3 with EIF4E, thus initiating translation. EIF4EBP1 mediates the regulation of protein translation in response to hormones, growth factors, and other stimuli that signal through the MAP kinase and mTORC1 pathways.

EIF4EBP1 is also known as 4E-BP1, 4EBP1, BP-1, PHAS-I.

Associated Diseases

WES Whole Exome Sequencing