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Bcr is a negative regulator of the Wnt signalling pathway
Author(s) -
Ress Angelika,
Moelling Karin
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400536
Subject(s) - regulator , signalling , wnt signaling pathway , microbiology and biotechnology , negative regulator , biology , breakpoint cluster region , signal transduction , genetics , gene
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.