Kaiso is a bimodal modulator for Wnt/beta-catenin signaling.
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 beta-catenin-complex formation. Our studies together provide insights into why Kaiso null mice display resistance to intestinal tumors when crossed onto an Apc(Min/+) background.
Mesh Terms:
Animals, Cell Line, DNA, Complementary, Embryo, Nonmammalian, Female, Gene Expression Regulation, Developmental, Genes, Reporter, Humans, Kidney, Luciferases, Renilla, Microinjections, Oligonucleotides, Antisense, Oocytes, Organ Culture Techniques, Plasmids, Repressor Proteins, Signal Transduction, Wnt Proteins, Xenopus Proteins, Xenopus laevis, beta Catenin
Animals, Cell Line, DNA, Complementary, Embryo, Nonmammalian, Female, Gene Expression Regulation, Developmental, Genes, Reporter, Humans, Kidney, Luciferases, Renilla, Microinjections, Oligonucleotides, Antisense, Oocytes, Organ Culture Techniques, Plasmids, Repressor Proteins, Signal Transduction, Wnt Proteins, Xenopus Proteins, Xenopus laevis, beta Catenin
FEBS Lett.
Date: Feb. 18, 2009
PubMed ID: 19166851
View in: Pubmed Google Scholar
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