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http://purl.uniprot.org/citations/25183871http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25183871http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25183871http://www.w3.org/2000/01/rdf-schema#comment"Canonical β-catenin-dependent Wnt signal transduction is important for several biological phenomena, such as cell fate determination, cell proliferation, stem cell maintenance and anterior-posterior axis formation. The hallmark of canonical Wnt signaling is the translocation of β-catenin into the nucleus where it activates gene transcription. However, the mechanisms regulating β-catenin nuclear localization are poorly understood. We show that Simplet/Fam53B (Smp) is required for Wnt signaling by positively regulating β-catenin nuclear localization. In the zebrafish embryo, the loss of smp blocks the activity of two β-catenin-dependent reporters and the expression of Wnt target genes, and prevents nuclear accumulation of β-catenin. Conversely, overexpression of smp increases β-catenin nuclear localization and transcriptional activity in vitro and in vivo. Expression of mutant Smp proteins lacking either the nuclear localization signal or the β-catenin interaction domain reveal that the translocation of Smp into the nucleus is essential for β-catenin nuclear localization and Wnt signaling in vivo. We also provide evidence that mammalian Smp is involved in regulating β-catenin nuclear localization: the protein colocalizes with β-catenin-dependent gene expression in mouse intestinal crypts; siRNA knockdown of Smp reduces β-catenin nuclear localization and transcriptional activity; human SMP mediates β-catenin transcriptional activity in a dose-dependent manner; and the human SMP protein interacts with human β-catenin primarily in the nucleus. Thus, our findings identify the evolutionary conserved SMP protein as a regulator of β-catenin-dependent Wnt signal transduction."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.org/dc/terms/identifier"doi:10.1242/dev.108415"xsd:string
http://purl.uniprot.org/citations/25183871http://purl.org/dc/terms/identifier"doi:10.1242/dev.108415"xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Kuchler B."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Kuechler B."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Kuechler B."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Brand M."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Brand M."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Weidinger G."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Weidinger G."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Antos C.L."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Antos C.L."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Argenton F."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Argenton F."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Kizil C."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Kizil C."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Moro E."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Moro E."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Oezhan G."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Oezhan G."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Yan J.J."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Yan J.J."xsd:string
http://purl.uniprot.org/citations/25183871http://purl.uniprot.org/core/author"Ozhan G."xsd:string