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- W2077408222 abstract "The canonical Wnt/β-catenin (Wnt) pathway is a master transcriptional regulatory signaling pathway that controls numerous biological processes including proliferation and differentiation. As such, transcriptional activity of the Wnt pathway is tightly regulated and/or modulated by numerous proteins at the level of the membrane, cytosol and/or nucleus. In the nucleus, transcription of Wnt target genes by TCF/LEF-1 is repressed by the long Groucho/TLE co-repressor family. However, a truncated member of the Groucho/TLE family, amino terminal enhancer of Split (AES) can positively modulate TCF/LEF-1 activity by antagonizing long Groucho/TLE members in a dominant negative manner. We have previously shown the soluble intracellular domain of the LRP6 receptor, a receptor required for activation of the Wnt pathway, can positively regulate transcriptional activity within the Wnt pathway. In the current study, we show the soluble LRP6 intracellular domain (LRP6-ICD) can also translocate to the nucleus in CHO and HEK 293T cells and in contrast to cytosolic LRP6-ICD; nuclear LRP6-ICD represses TCF/LEF-1 activity. In agreement with previous reports, we show AES enhances TCF/LEF-1 mediated reporter transcription and further we demonstrate that AES activity is spatially regulated in HEK 293T cells. LRP6-ICD interacts with AES exclusively in the nucleus and represses AES mediated TCF/LEF-1 reporter transcription. These results suggest that LRP6-ICD can differentially modulate Wnt pathway transcriptional activity depending upon its subcellular localization and differential protein-protein interactions." @default.
- W2077408222 created "2016-06-24" @default.
- W2077408222 creator A5025207687 @default.
- W2077408222 creator A5090842462 @default.
- W2077408222 date "2010-07-28" @default.
- W2077408222 modified "2023-09-23" @default.
- W2077408222 title "Differential Modulation of TCF/LEF-1 Activity by the Soluble LRP6-ICD" @default.
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- W2077408222 doi "https://doi.org/10.1371/journal.pone.0011821" @default.
- W2077408222 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2911377" @default.
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