Eukaryotic Initiation Factor 4E (eIF4E) sequestration mediates 4E-BP1 response to rapamycin.

The cap dependent translation initiation is a tightly controlled process of cooperative ternary complex formation by 4E-BP1, eIF4E and the 5' cap of eukaryotic mRNA in response to environmental cues like glucose, nutrients and growth factor levels. Based on the well-described effects of mTORC1/rapamycin complex on 4E-BP1 phosphorylation/s, it is generally accepted that rapamycin is a global inhibitor of cap-dependent translation. We have previously shown that 4E-BP1 resistance to rapamycin was overcome by the stoichiometric abundance of S6K1.