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.
Publication types
-
Comparative Study
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Blotting, Western / methods
-
Body Patterning / genetics
-
Body Patterning / physiology
-
Chromatin Immunoprecipitation / methods
-
Cloning, Molecular / methods
-
Cytoskeletal Proteins / metabolism*
-
Dose-Response Relationship, Drug
-
Drug Interactions
-
Electrophoretic Mobility Shift Assay / methods
-
Fluorescent Antibody Technique / methods
-
Gene Expression Regulation, Developmental / drug effects
-
Gene Expression Regulation, Developmental / physiology*
-
Homeodomain Proteins / genetics
-
Homeodomain Proteins / metabolism
-
Humans
-
Immunoprecipitation / methods
-
In Situ Hybridization / methods
-
Microinjections / methods
-
Mutation / physiology
-
Oligodeoxyribonucleotides, Antisense / pharmacology
-
RNA, Messenger / metabolism
-
Repressor Proteins / metabolism*
-
Reverse Transcriptase Polymerase Chain Reaction / methods
-
Signal Transduction / drug effects
-
Signal Transduction / physiology
-
Trans-Activators / metabolism*
-
Transcription, Genetic / drug effects
-
Transcription, Genetic / physiology*
-
Transforming Growth Factor beta / genetics
-
Transforming Growth Factor beta / metabolism
-
Xenopus Proteins / genetics
-
Xenopus Proteins / metabolism*
-
Xenopus Proteins / physiology*
-
Xenopus laevis
-
beta Catenin
Substances
-
CTNNB1 protein, Xenopus
-
CTNNB1 protein, human
-
Cytoskeletal Proteins
-
Homeodomain Proteins
-
Oligodeoxyribonucleotides, Antisense
-
RNA, Messenger
-
Repressor Proteins
-
SIA1 protein, Xenopus
-
Trans-Activators
-
Transforming Growth Factor beta
-
Xenopus Proteins
-
ZBTB33 protein, Xenopus
-
beta Catenin
-
nodal3.1 protein, Xenopus