A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation.
beta-Catenin is efficiently phosphorylated by glycogen synthase kinase-3beta in the Axin complex in the cytoplasm, resulting in the down-regulation. In response to Wnt, beta-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 beta-catenin in the nucleus. Duplin was located in the nucleus. Duplin bound directly to the Armadillo repeats of beta-catenin, thereby inhibiting the binding of Tcf to beta-catenin. It did not affect the stability of beta-catenin but inhibited Wnt- or beta-catenin-dependent Tcf activation. Furthermore, expression of Duplin in Xenopus embryos inhibited the axis formation and beta-catenin-dependent axis duplication, and prevented the beta-catenin's ability to rescue ventralizing phenotypes induced by ultraviolet light irradiation. Thus, Duplin is a nuclear protein that inhibits beta-catenin signaling.
Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, PRESTO, Japan.
I
I
Sakamoto
S
S
Kishida
A
A
Fukui
M
M
Kishida
H
H
Yamamoto
S
S
Hino
T
T
Michiue
S
S
Takada
M
M
Asashima
A
A
Kikuchi
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D019556:COS Cells; D015820:Cadherins / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000502:physiology; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D018411:Spodoptera; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D002352:Carrier Proteins; C415830:Chd8 protein, rat; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D051820:TCF Transcription Factors; C544895:Tcf7l2 protein, mouse; C553059:Tcf7l2 protein, rat; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D029867:Xenopus Proteins; D051176:beta Catenin; C544896:tcf7l2 protein, Xenopus; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3