BP75, bromodomain-containing M(r) 75,000 protein, binds dishevelled-1 and enhances Wnt signaling by inactivating glycogen synthase kinase-3 beta.
To identify novel regulators of Wnt signaling, we performed yeast two-hybrid analyses with Dvl-1 and identified BP75 as a candidate. Here, we demonstrated that BP75 directly interacts with Dvl-1 in mammalian cells and enhances TCF-dependent gene expression induced by Dvl-1. In support of these results, BP75 in cooperation with Dvl-1 ... was found to facilitate dephosphorylation at Tyr216 of glycogen synthase kinase-3beta and consequently inhibit its kinase activity. Furthermore, the nuclear translocation and formation of vesicular structures of beta-catenin were induced by BP75 and Dvl-1 in a synergistic manner. Collectively, these results provided us a novel mechanism in Wnt signaling where BP75 plays important regulatory roles between glycogen synthase kinase-3beta and Dvl.
Mesh Terms:
Active Transport, Cell Nucleus, Adaptor Proteins, Signal Transducing, Animals, COS Cells, Carrier Proteins, Chromosomal Proteins, Non-Histone, Cytoskeletal Proteins, DNA-Binding Proteins, Glycogen Synthase Kinase 3, Humans, Nerve Tissue Proteins, Nuclear Proteins, Phosphoproteins, Phosphorylation, Proto-Oncogene Proteins, TCF Transcription Factors, Trans-Activators, Transcription Factors, Transcription, Genetic, Wnt Proteins, Zebrafish Proteins, beta Catenin
Active Transport, Cell Nucleus, Adaptor Proteins, Signal Transducing, Animals, COS Cells, Carrier Proteins, Chromosomal Proteins, Non-Histone, Cytoskeletal Proteins, DNA-Binding Proteins, Glycogen Synthase Kinase 3, Humans, Nerve Tissue Proteins, Nuclear Proteins, Phosphoproteins, Phosphorylation, Proto-Oncogene Proteins, TCF Transcription Factors, Trans-Activators, Transcription Factors, Transcription, Genetic, Wnt Proteins, Zebrafish Proteins, beta Catenin
Cancer Res.
Date: Aug. 15, 2003
PubMed ID: 12941796
View in: Pubmed Google Scholar
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