Eukaryotic initiation factor 6 selectively regulates Wnt signaling and β-catenin protein synthesis

Eukaryotic initiation factor 6 (eIF6), an essential protein important in ribosome biosynthesis and assembly, was identified as an interacting partner of the β-catenin C terminus in the yeast two-hybrid assay. Independent studies identified Drosophila eIF6 (DeIF6) in a genetic screen designed to detect new genes involved in the regulation of the Wnt/Wg (wingless) pathway. Ectopic expression of DeIF6 in wing discs results in a Wg phenotype. Expression of eIF6 in adenomatous polyposis coli (APC)-mutant colon cancer cells, which express high levels of active β-catenin, showed that eIF6 selectively inhibits the Wnt pathway at the level of β-catenin protein independently of proteasomal degradation. Incorporation of radiolabeled amino acids into β-catenin was selectively decreased in cells that overexpressed eIF6. A similar inverse relationship of the two proteins was observed in the APC min/+ mouse intestine, in which β-catenin levels are very high. Taken together these data reveal a link between eIF6 and Wnt signaling, perhaps at the level of ribosome recycling on β-catenin mRNA.