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EMBO reports 6, 11, 1095–1100 (2005)
doi:10.1038/sj.embor.7400536
AOP Published online: 7 October 2005
Bcr is a negative regulator of the Wnt signalling pathway
Angelika Ress1, 2 & Karin Moelling1, 2
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1 Institute of Medical Virology, University of Zurich, Gloriastrasse 30, 8006 Zurich, Switzerland
2 Institute of Biochemistry, FU Berlin, Thielallee 63, 14195 Berlin, Germany
To whom correspondence should be addressed
Karin Moelling Tel: +41 44 634 26 52/53; Fax: +41 44 634 49 67; E-mail: moelling@immv.unizh.ch
Received 18 February 2005; Accepted 18 August 2005; Published online 7 October 2005.
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Abstract
The Wnt signalling pathway can activate transcription of genes such as c-myc through  -catenin. Here, we describe the protein breakpoint cluster region, Bcr, as a negative regulator of this pathway. Bcr can form a complex with -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 -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 -catenin. It phosphorylates Bcr in the first exon sequence on tyrosines, which abrogates the binding of Bcr to -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.
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