EIF4EBP1 Human

4E-BP1 functions as a translation repressor by binding to eIF4E, thereby inhibiting the assembly of the eIF4F complex, which is essential for the recruitment of the 40S ribosomal subunit to the 5’ end of mRNAs . This interaction effectively represses translation initiation. The phosphorylation state of 4E-BP1 determines its binding affinity to eIF4E. When 4E-BP1 is hypophosphorylated, it binds strongly to eIF4E and inhibits translation. Conversely, when 4E-BP1 is hyperphosphorylated, it dissociates from eIF4E, allowing the formation of the eIF4F complex and the initiation of translation .

The phosphorylation of 4E-BP1 is regulated by various signaling pathways, including the mechanistic target of rapamycin complex 1 (mTORC1) pathway . mTORC1 is a nutrient-responsive hub that regulates cell growth and metabolism. Upon activation by nutrients, growth factors, or other stimuli, mTORC1 phosphorylates 4E-BP1 at multiple sites, leading to its dissociation from eIF4E and the subsequent activation of cap-dependent translation .

4E-BP1 is involved in several critical biological processes, including the regulation of cell growth, proliferation, and survival . It plays a role in the insulin signaling pathway, cellular response to stress, and the regulation of the mitotic cell cycle . Additionally, 4E-BP1 has been implicated in various diseases, including cancer, where its dysregulation can lead to uncontrolled cell growth and proliferation .

Given its central role in translation regulation, 4E-BP1 is a potential target for therapeutic interventions in diseases characterized by aberrant protein synthesis, such as cancer . Understanding the mechanisms that regulate 4E-BP1 activity and its interactions with eIF4E can provide insights into the development of novel therapeutic strategies.