Bcr is a negative regulator of the Wnt signalling pathway

• Published in: EMBO reports Vol. 6; no. 11; pp. 1095 - 1100
• Main Authors: Ress, Angelika, Moelling, Karin
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.11.2005; Blackwell Publishing Ltd
• Subjects: Bcr; Bcr-Abl; Benzamides; beta Catenin - genetics; beta Catenin - metabolism; Cell Line, Tumor; Fusion Proteins, bcr-abl - metabolism; Gene Expression Regulation; Genes, myc - physiology; Gleevec; Humans; Imatinib Mesylate; Myc; Phosphorylation - drug effects; Piperazines - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-bcr - genetics; Proto-Oncogene Proteins c-bcr - metabolism; Pyrimidines - pharmacology; RNA Interference; Scientific Report; Signal Transduction; STI-571; Transcription, Genetic; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; tumour suppressor; Wnt Proteins - physiology; β-catenin
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/sj.embor.7400536

The Wnt signalling pathway can activate transcription of genes such as c‐myc through β‐catenin. Here, we describe the protein breakpoint cluster region, Bcr, as a negative regulator of this pathway. Bcr can form a complex with β‐catenin and negatively regulate expression of c‐Myc. Knockdown of Bcr by short interfering RNA relieves the block and activates expression of c‐Myc. Expression of Bcr in the human colon carcinoma cell line HCT116, which has a high level of endogenous β‐catenin, leads to reduced c‐Myc expression. The negative effect is exerted by the amino terminus of Bcr, which does not harbour the kinase domain. Bcr‐Abl, the oncogene protein expressed in chronic myelogenous leukaemia (CML), does not bind to β‐catenin. It phosphorylates Bcr in the first exon sequence on tyrosines, which abrogates the binding of Bcr to β‐catenin. The inhibitor of the Bcr–Abl tyrosine kinase, STI‐571 or Gleevec, a drug against CML, reverses this effect. Our data contribute to the understanding of Bcr as a tumour suppressor in the Wnt signalling pathway, as well as in CML.