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Sci Rep 2017 Feb 15;7:42590. doi: 10.1038/srep42590.
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Ubiquitin C-terminal hydrolase37 regulates Tcf7 DNA binding for the activation of Wnt signalling.

Han W , Lee H , Han JK .

The Tcf/Lef family of transcription factors mediates the Wnt/β-catenin pathway that is involved in a wide range of biological processes, including vertebrate embryogenesis and diverse pathogenesis. Post-translational modifications, including phosphorylation, sumoylation and acetylation, are known to be important for the regulation of Tcf/Lef proteins. However, the importance of ubiquitination and ubiquitin-mediated regulatory mechanisms for Tcf/Lef activity are still unclear. Here, we newly show that ubiquitin C-terminal hydrolase 37 (Uch37), a deubiquitinase, interacts with Tcf7 (formerly named Tcf1) to activate Wnt signalling. Biochemical analyses demonstrated that deubiquitinating activity of Uch37 is not involved in Tcf7 protein stability but is required for the association of Tcf7 to target gene promoter in both Xenopus embryo and human liver cancer cells. In vivo analyses further revealed that Uch37 functions as a positive regulator of the Wnt/β-catenin pathway downstream of β-catenin stabilization that is required for the expression of ventrolateral mesoderm genes during Xenopus gastrulation. Our study provides a new mechanism for chromatin occupancy of Tcf7 and uncovers the physiological significance of Uch37 during early vertebrate development by regulating the Wnt/β-catenin pathway.

PubMed ID: 28198400
PMC ID: PMC5309806
Article link: Sci Rep

Species referenced: Echinodermata
Genes referenced: gscl jun LOC100147806 LOC105439774 LOC105442066 LOC115919910 LOC115921693 LOC373385 LOC587333 LOC590297 LOC594349 LOC594353 mos myod1l Tcf/Lef wnt8a

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References [+] :
Arce, Diversity of LEF/TCF action in development and disease. 2006, Pubmed