title: The Krüppel-like zinc finger protein Glis2 functions as a negative modulator of the Wnt/beta-catenin signaling pathway.
abstract: To gain insight into the mechanism by which Gli-similar 2 (Glis2) regulates transcription, we performed yeast-two hybrid cDNA library screening using Glis2 as bait. This screening identified beta-catenin as a potential Glis2-interacting protein. Mammalian two-hybrid, co-immunoprecipitation, and GST-pulldown analyses supported the interaction between Glis2 and beta-catenin. Pulldown analyses with several Glis2 deletion mutants indicated that the 1st zinc finger motif of Glis2 is critical for its interaction with beta-catenin, while the armadillo repeats of beta-catenin are important in its interaction with Glis2. Reporter analyses showed that Glis2 represses T-cell factor (TCF)-mediated transcriptional activation. In addition, Glis2 represses the expression of the TCF target gene cyclin D1. Our results indicate that Glis2 interacts with beta-catenin and suggest that Glis2 functions as a negative modulator of beta-catenin/TCF-mediated transcription.
authors.affiliation: Cell Biology Section, LRB, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Yong-Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Hong Soon
authors.initials: HS
authors.lastname: Kang
authors.forename: Anton M
authors.initials: AM
authors.lastname: Jetten
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers; D051176:beta Catenin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D056741:Cyclin D; D016213:Cyclins; C447919:GLIS2 protein, human; D051741:Kruppel-Like Transcription Factors; D011994:Recombinant Proteins; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin