Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.
Wnt signaling plays a crucial role in a number of developmental processes and in tumorigenesis. beta-Catenin is stabilized by Wnt signaling and associates with the TCF/LEF family of transcription factors, thereby activating transcription of Wnt target genes. Constitutive activation of beta-catenin-TCF-mediated transcription resulting from mutations in adenomatous polyposis coli (APC), beta-catenin, or Axin is believed to be a critical step in tumorigenesis among divergent types of cancers. Here we show that the transactivation potential of the beta-catenin-TCF complex is enhanced by its interaction with a BCL9-like protein, B9L, in addition to BCL9. We found that B9L is required for enhanced beta-catenin-TCF-mediated transcription in colorectal tumor cells and for beta-catenin-induced transformation of RK3E cells. Furthermore, expression of B9L was aberrantly elevated in about 43% of colorectal tumors, relative to the corresponding noncancerous tissues. These results suggest that B9L plays an important role in tumorigenesis induced by aberrant activation of Wnt signaling.
Pubmed ID: 15574752 RIS Download
Amino Acid Sequence | Animals | Cell Transformation, Neoplastic | Colorectal Neoplasms | Cytoskeletal Proteins | DNA-Binding Proteins | Humans | Immunohistochemistry | Intercellular Signaling Peptides and Proteins | Lymphoid Enhancer-Binding Factor 1 | Molecular Sequence Data | Neoplasm Proteins | Protein Binding | Rats | Reverse Transcriptase Polymerase Chain Reaction | Signal Transduction | Trans-Activators | Transcription Factors | Transcription, Genetic | Transfection | Wnt Proteins | beta Catenin