Eukaryotic initiation factor 6 selectively regulates Wnt signaling and beta-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 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.
Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC 20057, USA.
Y
Y
Ji
S
S
Shah
K
K
Soanes
M N
MN
Islam
B
B
Hoxter
S
S
Biffo
T
T
Heslip
S
S
Byers
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010448:Peptide Initiation Factors / Q000032:analysis / Q000378:metabolism*; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014921:Wings, Animal / Q000254:growth & development; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051176:beta Catenin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D025601:Adenomatous Polyposis Coli Protein; D000596:Amino Acids; D029721:Drosophila Proteins; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin; C021019:eIF-6