The Effect of eIF4G Inhibitor SBI-756 on eIF4F Complex Formation

Background: Translation initiation is the rate-limiting step in protein synthesis. The cap-dependent translation initiation complex eIF4F is required foxr unwinding secondary structures in mRNA 5’UTRs and for ribosome recruitment. The eIF4F complex consists of three proteins: eIF4G (scaffolding protein), eIF4E (cap-binding protein) and eIF4A (RNA helicase). Since various oncogenes contain a complex 5’UTR, the eIF4F initiation complex controls their expression levels, making it a key regulator in cancer development. Furthermore, overexpression of eIF4F is often correlated with many cancers. Hence, eIF4F is considered as a promising target for cancer patient treatments, especially combined with drugs against its upstream regulators to circumvent drug-acquired resistance. With this vision, our collaborators developed SBI-756, a small molecule inhibitor that targets eIF4G protein.

Methods: Using immunofluorescence staining and confocal microscope imaging, our study focusses on the effect of SBI-756 treatments on the localization of eIF4E and eIF4G and on their interactions. Our algorithm can quantify the labeled proteins localized to stress granules or p-bodies- foci that form in cells due to different drug treatments.

Results: SBI-756 treatment alters eIF4G and eIF4E localizations, suggesting that it interferes with eIF4F complex formation.