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PMID: 15371335 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions.

Genes & development ·Vol. 18 ·No. 18 ·2004-09-15 ·Pages 2225-30

Brembeck FH, Schwarz-Romond T, Bakkers J, Wilhelm S, Hammerschmidt M, Birchmeier W

Abstract

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.

MeSH Terms
Animals Body Patterning Carrier Proteins/physiology Cell Adhesion/physiology Cell Line, Transformed Cell Membrane/metabolism Cell Movement Cell Nucleus/metabolism Cells, Cultured Cytoskeletal Proteins/genetics,metabolism Embryo, Nonmammalian Epithelial Cells/physiology Humans Mesoderm/cytology,physiology Mice Neoplasm Proteins/physiology Phosphorylation Protein Transport/physiology Proteins/metabolism Proto-Oncogene Mas RNA Interference Sequence Homology, Amino Acid Trans-Activators/genetics,metabolism Transcription Factors Transcription, Genetic Tyrosine/metabolism Wnt Proteins Zebrafish/embryology Zebrafish Proteins beta Catenin
Chemicals
BCL9 protein, human CTNNB1 protein, human CTNNB1 protein, mouse Carrier Proteins Cytoskeletal Proteins MAS1 protein, human Neoplasm Proteins Proteins Proto-Oncogene Mas Trans-Activators Transcription Factors Wnt Proteins Zebrafish Proteins bcl9l protein, zebrafish beta Catenin ctnnb1 protein, zebrafish wnt8a protein, zebrafish Tyrosine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Brembeck Felix H
Max Delbrueck Center for Molecular Medicine, 13092 Berlin, Germany.
Schwarz-Romond Thomas
Bakkers Jeroen
Wilhelm Sabine
Hammerschmidt Matthias
Birchmeier Walter
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.317604
Published
2004-09-15
Epub
2004-00-01
Pages
2225-30
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC517514
Subset
IM
Grants
NIGMS NIH HHS · R01 GM063904 · United States
NIGMS NIH HHS · R01 GM063904-01 · United States
NIGMS NIH HHS · 1R01 GM63904 · United States
External Links
PubMed source DOI: 10.1101/gad.317604 PMC Full Text View journal details
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