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Sci Rep January 1, 2017; 7 42590.

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: Xenopus
Genes referenced: adrm1 bmp4 ccnd1 chrd.1 ctnnb1 dvl2 fgf4 gsc lef1 lrp6 msx1 myc myod1 nodal1 nodal3.4 odc1 post prl.2 sia1 szl tbxt tcf7 tcf7l1 uchl5 ventx1.2 ventx2.2 wnt8a xpo1
Morpholinos: uchl5 MO1

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