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Oncogene. 2008 Jan 31;27(6):755-62. Epub 2007 Jul 30.

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

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  • 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC 20057, USA.

Abstract

Eukaryotic initiation factor 6 (eIF6), an essential protein important in ribosome biosynthesis and assembly, was identified as an interacting partner of the beta-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 beta-catenin, showed that eIF6 selectively inhibits the Wnt pathway at the level of beta-catenin protein independently of proteasomal degradation. Incorporation of radiolabeled amino acids into beta-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 beta-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 beta-catenin mRNA.

PMID:
17667944
[PubMed - indexed for MEDLINE]
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