Wnt/Beta-catenin pathway and associated ncRNAs

Wnt/β-catenin pathway and associated ncRNAs. When the Wnt signaling pathway is not effectively inhibited by Dickkopf (DKK) or Wnt inhibitory protein (WIF), which interact with lipoprotein receptor-related 5/6 (LRP5/6) to disrupt LRP5/6 and Frizzled (FZD) receptor dimers, Wnt proteins are able to bind to their FZD receptors, leading to dimerization of FZD and LRP5/6 receptors. The formation of FZD/LRP heterodimers induces a conformational change in the receptors, leading to the binding of the cytoplasmic portion of FZD to disheveled (DVL) and phosphorylation of the LRP5/6 tail by GSK3. This phosphorylation event facilitates the recruitment of the scaffold protein Axin. DVL serves as a platform for enhanced interaction between Axin and the LRP5/6 tail. The interaction between Axin, LRP5/6, and DVL disrupts the Destructive Complex (DC), releasing β-catenin. Subsequently, β-catenin translocates into the nucleus, where it displaces corepressor Groucho/transducin with TCF/LEF to form a complex that mediates gene expression. The destruction complex (DC), composed of Axin, adenomatous polyposis (APC), glycogen synthase kinase 3β (GSK3β), and casein kinase 1ɑ (CK1ɑ), functions to maintain β-catenin in an inactive state through phosphorylation by CK1ɑ, facilitating GSK3β-mediated phosphorylation of β-catenin. Subsequent phosphorylation of β-catenin leads to recruitment of β-transducin repeat containing protein (β-Trcp), an E3 ubiquitin ligase that promotes ubiquitination of β-catenin for degradation. The Wnt/β-catenin pathway is also regulated by various ncRNAs

Publication

Noncoding RNA-Mediated Epigenetic Regulation in Hepatic Stellate Cells of Liver Fibrosis (2024) Ruoyu Gao, et al. Noncoding RNA. 2024 Aug;10(4). Figure: F5. Homo sapiens

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