Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets.
Beta-catenin-dependent or canonical Wnt signals are fundamental in animal development and tumor progression. Using Xenopus laevis, we report that the BTB/POZ zinc finger family member Kaiso directly represses canonical Wnt gene targets (Siamois, c-Fos, Cyclin-D1, and c-Myc) in conjunction with TCF/LEF (TCF). Analogous to beta-catenin relief of TCF repressive activity, we show that p120-catenin relieves Kaiso-mediated repression of Siamois. Furthermore, Kaiso and TCF coassociate, and combined Kaiso and TCF derepression results in pronounced Siamois expression and increased beta-catenin coprecipitation with the Siamois promoter. The functional interdependency is underlined by Kaiso suppression of beta-catenin-induced axis duplication and by TCF-3 rescue of Kaiso depletion phenotypes. These studies point to convergence of parallel p120-catenin/Kaiso and beta-catenin/TCF signaling pathways to regulate gene expression in vertebrate development and possibly carcinogenesis.
Park
Jae-Il
JI
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Kim
Si Wan
SW
Lyons
Jon P
JP
Ji
Hong
H
Nguyen
Thi T
TT
Cho
Kyucheol
K
Barton
Michelle C
MC
Deroo
Tom
T
Vleminckx
Kris
K
Moon
Randall T
RT
McCrea
Pierre D
PD
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D047369:Chromatin Immunoprecipitation / Q000379:methods; D003001:Cloning, Molecular / Q000379:methods; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008845:Microinjections / Q000379:methods; D009154:Mutation / Q000502:physiology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014982:Xenopus laevis; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D012097:Repressor Proteins; C093133:SIA1 protein, Xenopus; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C451401:ZBTB33 protein, Xenopus; D051176:beta Catenin; C094620:nodal3.1 protein, Xenopus