The Hsp90 Inhibitor Geldanamycin Abrogates Colocalization of eIF4E and eIF4E-Transporter into Stress Granules and Association of eIF4E with eIF4G

The eukaryotic translation initiation factor eIF4Eplays a critical role in the control of translation initiation through binding to the mRNA 5′ cap structure. eIF4Eis also a component of processing bodies and stress granules, which are two types of cytoplasmic RNA granule in which translationally inactivated mRNAs accumulate. We found that treatment with the Hsp90 inhibitor geldanamycinleads to a substantial reduction in the number of HeLa cells that contain processing bodies. In contrast, stress granulesare not disrupted but seem to be only partially affected by the inhibition of Hsp90. However, it is striking that eIF4Eas well as its binding partner eIF4Etransporter (4E-T), which mediates the import of eIF4Einto the nucleus, are obviously lost from stress granules. Furthermore, the amount of eIF4Gthat is associated with the cap via eIF4Eis reduced by geldanamycintreatment. Thus, the chaperone activity of Hsp90probably contributes to the correct localization of eIF4Eand 4E-T to stress granulesand also to the interaction between eIF4Eand eIF4G, both of which may be needed for eIF4Eto acquire the physiological functionality that underlies the mechanism of translation initiation.