| | Kaiso is a bimodal modulator for Wnt/β-catenin signalingEdited by Lukas Huber Received 11 August 2008; received in revised form 12 January 2009; accepted 12 January 2009. published online 21 January 2009. Abstract The Wnt family of secreted ligands plays critical roles during embryonic development and tumorigenesis. Here we show that Kaiso, a dual specific DNA-binding protein, functions as a bimodal regulator of canonical Wnt signaling. Loss-of-function analysis of Kaiso abrogated Wnt-mediated reporter activity and axis duplication, whereas gain-of-function analysis of Kaiso dose-dependently resulted in synergistic and suppressive effects. Our analyses further suggest Kaiso can regulate TCF/LEF1-activity for these effects via modulating HDAC1 and β-catenin-complex formation. Our studies together provide insights into why Kaiso null mice display resistance to intestinal tumors when crossed onto an ApcMin/+ background. Stuctured summaryMINT-6823807: HDAC1 (uniprotkb:Q13547) physically interacts (MI:0218) with beta catenin (uniprotkb:P35222) by anti tag coimmunoprecipitation (MI:0007) MINT-6823820: axin (uniprotkb:O15169) physically interacts (MI:0218) with beta catenin (uniprotkb:P35222) by anti tag coimmunoprecipitation (MI:0007) BRB 723, Department of Genetics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, United States  Corresponding author. Fax: +1 216 368 0491.
PII: S0014-5793(09)00039-8 doi:10.1016/j.febslet.2009.01.012 © 2009 Federation of European Biochemical Societies | |
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ABSTRACT
