Study on the ubiquitination of Tcf7 for Wnt signaling during Xenopus embryogenesis

DoctorThe Tcf/Lef family of transcription factors mediates Wnt/ß-catenin signaling, which is involved in a wide range of biological processes such as vertebrate embryogenesis, cell proliferation, tissue homeostasis and diverse pathogeneses. Post-translational modifications, including phosphorylation, sumoylation and acetylation have been suggested as an important regulatory mechanism for transcriptional activity of Tcf/Lef family. However, the ubiquitination-mediated Tcf/Lef regulation is still unclear. In this study, I newly report that ubiquitin Cterminal hydrolase 37 (Uch37), a deubiquitinase, interacts with Tcf7 (formerly named Tcf1) to activate Wnt/ß-catenin signaling. Biochemical analyses demonstrated that Uch37 modulates polyubiquitination of Tcf7 protein, which has a non-proteolytic function. In addition, the deubiquitinating activity of Uch37 is required for the association of Tcf7 to the target gene promoter in both Xenopus and human liver cancer cells. In vivo analyses using Xenopus embryo further revealed that Uch37 functions as a positive regulator of the Wnt/ß-catenin signaling downstream of the ß-catenin stabilization required for the expression of ventrolateral mesoderm genes during Xenopus gastrulation. This 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/ß-catenin pathway

Xenopus Ubiquitin carboxy-terminal hydrolase L5 (XUchL5) regulates XTcf1-mediated transcriptional activity in the Wnt/b-catenin pathway

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Involvement of Phospho-protein phosphatase4 Catalyitic Subunit in The Wnt/b-catenin pathway

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PP4c regulates anterior-posterior neural patterning in Xenopus Laevis as a positive regulator of Wnt/b-catenin signaling

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Phospho-protein phosphatase 4(PP4) regulates anterior-posterior neural patterning through Wnt/b-catenin signaling during Xenopus development

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XUch37 regulates the formation of XTcf/b-catenin complex for mediating Xenopus mesoderm patterning

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Uch37 mediates DNA binding of Tcf1 through its deubiquitinating activity during Xenopus gastrulation

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The role of Tbx2 in otic placode formation and invagination

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