Eukaryotic initiation factor 4E binding protein 1 (4E-BP1, MW: 20 kDa), also known as PHAS-I, is the predominant member of a family of eIF4E-binding proteins whose binding affinity to eIF4E is regulated by its phosphorylation. Besides its eIF4E-binding domain, two other motifs are important for 4E-BP1 function in vivo. One of these is a TOS motif (Phe-Glu-Met-Asp-Ile) located at the end of the carboxy-terminus, and the other is a RAIP motif (Arg-Als-Ile-Pro) at the amino-terminus.

Translation repressor protein 4E-BP1 (also known as PHAS-1) inhibits cap-dependent translation by binding to the translation initiation factor eIF4E. Hyperphosphorylation of 4E-BP1 disrupts this interaction and results in activation of cap-dependent translation (1). Both the PI3 kinase/Akt pathway and FRAP/mTOR kinase regulate 4E-BP1 activity (2,3). Multiple 4E-BP1 residues are phosphorylated in vivo (4). While phosphorylation by FRAP/mTOR at Thr37 and Thr46 does not prevent the binding of 4E-BP1 to eIF4E, it is thought to prime 4E-BP1 for subsequent phosphorylation at Ser65 and Thr70 (5).