ArticleScientific reports2023
RNF2 regulates Wnt/ß-catenin signaling via TCF7L1 destabilization.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 3 citations in OpenAlex.
- CPTCs Drive Somatic-Visceral Communication via the Wnt Axis in Somatic Mechanotherapy: A Single-Cell Deep Learning Study.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Indirubin treatment was associated with modulation of the PI3K/AKT and MAPK pathways and induction of apoptosis and autophagy.Scientific reports · 2026Article
- ONX-0914 Suppresses Hormone-Sensitive Prostate Cancer by Promoting O-GlcNAcylation-Mediated Stabilization of TCF7L1.Oncology research · 2026Article
- MEOX1-mediated transcriptional regulation of circABHD3 exacerbates hepatic fibrosis through promoting m6A/YTHDF2-dependent YPEL3 mRNA decay to activate β-catenin signaling.PLoS genetics · 2025Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
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Abstract
The Wnt signaling pathway is a crucial regulator of various biological processes, such as development and cancer. The downstream transcription factors in this pathway play a vital role in determining the threshold for signaling induction and the length of the response, which vary depending on the biological context. Among the four transcription factors involved in canonical Wnt/ß-catenin signaling, TCF7L1 is known to possess an inhibitory function; however, the underlying regulatory mechanism remains unclear. In this study, we identified the E3 ligase, RNF2, as a novel positive regulator of the Wnt pathway. Here, we demonstrate that RNF2 promotes the degradation of TCF7L1 through its ubiquitination upon activation of Wnt signaling. Loss-of-function studies have shown that RNF2 consistently destabilizes nuclear TCF7L1 and is required for proper Wnt target gene transcription in response to Wnt activation. Furthermore, our results revealed that RNF2 controls the threshold, persistence, and termination of Wnt signaling by regulating TCF7L1. Overall, our study sheds light on the previously unknown degradation mechanism of TCF7L1 by a specific E3 ligase, RNF2, and provides new insights into the variability in cellular responses to Wnt activation.
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