AI Article Synopsis
- TCF/LEF factors are key proteins that control embryonic development and stem cell function, becoming active through β-catenin in response to Wnt signaling; their dysregulation can lead to cancer.
- The study identifies a complex called ChiLS that binds specifically to the NPF motif, also interacting with other nuclear factors, indicating its role in regulating protein interactions involved in Wnt signaling.
- Research on Wnt-responsive enhancers in Drosophila shows how these factors form a functional unit (enhanceosome) that adapts to various signals; ChiLS is essential for maintaining proper embryonic and stem cell activity, thereby preventing cancer.
Article Abstract
TCF/LEF factors are ancient context-dependent enhancer-binding proteins that are activated by β-catenin following Wnt signaling. They control embryonic development and adult stem cell compartments, and their dysregulation often causes cancer. β-catenin-dependent transcription relies on the NPF motif of Pygo proteins. Here, we use a proteomics approach to discover the Chip/LDB-SSDP (ChiLS) complex as the ligand specifically binding to NPF. ChiLS also recognizes NPF motifs in other nuclear factors including Runt/RUNX2 and Drosophila ARID1, and binds to Groucho/TLE. Studies of Wnt-responsive dTCF enhancers in the Drosophila embryonic midgut indicate how these factors interact to form the Wnt enhanceosome, primed for Wnt responses by Pygo. Together with previous evidence, our study indicates that ChiLS confers context-dependence on TCF/LEF by integrating multiple inputs from lineage and signal-responsive factors, including enhanceosome switch-off by Notch. Its pivotal function in embryos and stem cells explain why its integrity is crucial in the avoidance of cancer.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571689 | PMC |
| http://dx.doi.org/10.7554/eLife.09073 | DOI Listing |
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