title: Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Park
authors.forename: Si Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Jon P
authors.initials: JP
authors.lastname: Lyons
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Thi T
authors.initials: TT
authors.lastname: Nguyen
authors.forename: Kyucheol
authors.initials: K
authors.lastname: Cho
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Barton
authors.forename: Tom
authors.initials: T
authors.lastname: Deroo
authors.forename: Kris
authors.initials: K
authors.lastname: Vleminckx
authors.forename: Randall T
authors.initials: RT
authors.lastname: Moon
authors.forename: Pierre D
authors.initials: PD
authors.lastname: McCrea
mesh_terms: 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
chemical_list: 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