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

Abstract

Eukaryotic initiation factor 6 (eIF6), an essential protein important in ribosome biosynthesis and assembly, was identified as an interacting partner of the b-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 b-catenin, showed that eIF6 selectively inhibits the Wnt pathway at the level of b-catenin protein independently of proteasomal degradation. Incorporation of radiolabeled amino acids into b-catenin was selectively decreased in cells that overexpressed eIF6. A similar inverse relationship of the two proteins was observed in the APC min/ þ mouse intestine, in which b-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 b-catenin mRNA.

Helicobacter pylori in a Korean Isolate Expressed Proteins Differentially in Human Gastric Epithelial Cells

“…The results suggest that eIF6 has an important role in the cytoplasm. One of the roles of eIF6 is the interaction with an adhesion molecule integrin-b4 [50]. In the present study, an increase in eIF6 by H. pylori infection shows its possible relationship to ribosome assembly for translation, cell proliferation, and cell adhesion.…”

p27BBP/eIF6 acts as an anti-apoptotic factor upstream of Bcl-2 during Xenopus laevis development

“…8,9 Recently, the study of p27 BBP /eIF6 has gained new interest because this protein seems to regulate the translation of specific mRNAs such as b-catenin mRNA, thus modulating the fundamental signaling of the Wnt/b-catenin pathway. 13 Moreover, it has been proposed that p27 BBP /eIF6 functions in miRNA-mediated post-transcriptional silencing because it is part of RNA-induced silencing complex (RISC) and as such, in Caenorhabditis elegans, it specifically represses the translation of LIN-14 and LIN-28 mRNAs without an effect on the general translation. 14 In other experimental systems, p27 BBP /eIF6 is not necessary for miRNA-based translational repression.…”

Eukaryotic initiation factor 6 modulates myofibroblast differentiation at transforming growth factor-β1 transcription level via H2A.Z occupancy and Sp1 recruitment

“…Although a positive role for eIF6 in global translation has been proved in knockdown mice, there is evidence for a selective role of eIF6 in gene regulation. In line with these data, eIF6 has been demonstrated to selectively regulate Wnt signaling and β-catenin protein synthesis (Ji et al, 2008). However, verification of this concept requires further study.…”

“…Dysregulation of eIF6 expression has proved to be relevant to some pathological states. Ectopic expression of Drosophila eIF6 (DeIF6) in wing discs results in a Wg phenotype due to eIF6 selectively regulating Wnt signaling and β-catenin protein synthesis (Ji et al, 2008). The injection of eIF6 mRNA into one blastomere of two-cell-stage embryos resulted in a bent phenotype and fewer apoptotic cells during Xenopus laevis development, because eIF6 seemed to regulate the translation of specific mRNAs as an anti-apoptotic factor (De Marco et al, 2010).…”