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.
Iioka
Hidekazu
H
BRB 723, Department of Genetics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Doerner
Stephanie K
SK
Tamai
Keiko
K
D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D004625:Embryo, Nonmammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006801:Humans; D007668:Kidney / Q000166:cytology; D049410:Luciferases, Renilla / Q000378:metabolism; D008845:Microinjections; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D009924:Organ Culture Techniques; D010957:Plasmids; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D012097:Repressor Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; C451401:ZBTB33 protein, Xenopus; D051176:beta Catenin; D049410:Luciferases, Renilla