| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2040071 | Cell Reports | 2013 | 9 Pages |
•β-catenin binding to Tcf7l1 causes displacement from chromatin and degradation•Reduced chromatin binding initiates β-catenin inactivation of Tcf7l1•Inactivation of Tcf7l1 is the only necessary function for Tcf7l1-β-catenin binding
SummaryWnt/β-catenin signal transduction requires direct binding of β-catenin to Tcf/Lef proteins, an event that is classically associated with stimulating transcription by recruiting coactivators. This molecular cascade plays critical roles throughout embryonic development and normal postnatal life by affecting stem cell characteristics and tumor formation. Here, we show that this pathway utilizes a fundamentally different mechanism to regulate Tcf7l1 (formerly named Tcf3) activity. β-catenin inactivates Tcf7l1 without a switch to a coactivator complex by removing it from DNA, which leads to Tcf7l1 protein degradation. Mouse genetic experiments demonstrate that Tcf7l1 inactivation is the only required effect of the Tcf7l1-β-catenin interaction. Given the expression of Tcf7l1 in pluripotent embryonic and adult stem cells, as well as in poorly differentiated breast cancer, these findings provide mechanistic insights into the regulation of pluripotency and the role of Wnt/β-catenin in breast cancer.
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