4EBPmediated

4E-BP-mediated regulation refers to the control of cap-dependent translation by eIF4E-binding proteins. In mammals, the primary family members are 4E-BP1, 4E-BP2, and 4E-BP3. These proteins bind to the cap-binding protein eIF4E, blocking its interaction with eIF4G and thereby repressing initiation of translation. This mechanism serves as a key node linking nutrient and growth signals to protein synthesis.

Activation of signaling pathways such as mTORC1 controls 4E-BP activity through phosphorylation. When nutrients and growth factors are abundant, mTORC1 phosphorylates 4E-BPs at multiple sites, decreasing their affinity for eIF4E and allowing assembly of the eIF4F complex (eIF4E–eIF4G–eIF4A) to initiate translation. Under stress, energy depletion, or pharmacological inhibition of mTOR, 4E-BPs become hypophosphorylated, bind tightly to eIF4E, and repress cap-dependent translation.

4E-BP–mediated control affects global protein synthesis and can influence selective translation of certain mRNAs, particularly those with complex 5'UTRs or TOP motifs, thereby shaping cell growth, metabolism, and stress responses.

Dysregulation of 4E-BP signaling has been observed in cancer and metabolic diseases. Pharmacologic mTOR inhibitors promote 4E-BP–mediated repression of translation, and changes in 4E-BP phosphorylation status are used as a readout of mTOR activity in research and clinical contexts.