Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions.
beta-Catenin controls both cadherin-mediated cell adhesion and activation of Wnt target genes. We demonstrate here that the beta-catenin-binding protein BCL9-2, a homolog of the human proto-oncogene product BCL9, induces epithelial-mesenchymal transitions of nontransformed cells and increases beta-catenin-dependent transcription. RNA interference of BCL9-2 in carcinoma cells induces an epithelial phenotype and translocates beta-catenin from the nucleus to the cell membrane. The switch between beta-catenin's adhesive and transcriptional functions is modulated by phosphorylation of Tyr 142 of beta-catenin, which favors BCL9-2 binding and precludes interaction with alpha-catenin. During zebrafish embryogenesis, BCL9-2 acts in the Wnt8-signaling pathway and regulates mesoderm patterning.
Brembeck
Felix H
FH
Max Delbrueck Center for Molecular Medicine, 13092 Berlin, Germany.
Schwarz-Romond
Thomas
T
Bakkers
Jeroen
J
Wilhelm
Sabine
S
Hammerschmidt
Matthias
M
Birchmeier
Walter
W
D000818:Animals; D019521:Body Patterning; D002352:Carrier Proteins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism; D051153:Wnt Proteins; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins; D051176:beta Catenin
C111180:BCL9 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D011506:Proteins; D000090063:Proto-Oncogene Mas; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C492660:bcl9l protein, zebrafish; D051176:beta Catenin; C495269:ctnnb1 protein, zebrafish; C094521:wnt8a protein, zebrafish; D014443:Tyrosine