A Novel β-Catenin-binding Protein Inhibits β-Catenin-dependent Tcf Activation and Axis Formation

• Published in: The Journal of biological chemistry 2000-10, Vol.275 (42), p.32871-32878
• Main Authors: Sakamoto, Ikuo, Kishida, Shosei, Fukui, Akimasa, Kishida, Michiko, Yamamoto, Hideki, Hino, Shin-ichiro, Michiue, Tatsuo, Takada, Shinji, Asashima, Makoto, Kikuchi, Akira
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; beta Catenin; Body Patterning - physiology; Cadherins - metabolism; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line; Cell Nucleus - physiology; COS Cells; Cytoskeletal Proteins - metabolism; Embryo, Nonmammalian - physiology; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases; L Cells; Mice; Molecular Sequence Data; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Recombinant Proteins - metabolism; Spodoptera; TCF Transcription Factors; Trans-Activators; Transcription Factor 7-Like 2 Protein; Transcription Factors - metabolism; Transfection; Xenopus laevis - embryology; Xenopus Proteins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M004089200

β-Catenin is efficiently phosphorylated by glycogen synthase kinase-3β in the Axin complex in the cytoplasm, resulting in the down-regulation. In response to Wnt, β-catenin is stabilized and translocated into the nucleus where it stimulates gene expression through Tcf/Lef. Here we report a novel protein, designated Duplin (for axis duplication inhibitor), which negatively regulates the function of β-catenin in the nucleus. Duplin was located in the nucleus. Duplin bound directly to the Armadillo repeats of β-catenin, thereby inhibiting the binding of Tcf to β-catenin. It did not affect the stability of β-catenin but inhibited Wnt- or β-catenin-dependent Tcf activation. Furthermore, expression of Duplin in Xenopus embryos inhibited the axis formation and β-catenin-dependent axis duplication, and prevented the β-catenin's ability to rescue ventralizing phenotypes induced by ultraviolet light irradiation. Thus, Duplin is a nuclear protein that inhibits β-catenin signaling.