The Krueppel-like zinc finger protein Glis2 functions as a negative modulator of the Wnt/beta-catenin signaling pathway.
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.
Mesh Terms:
Cell Line, Cell Nucleus, Cyclin D, Cyclins, Humans, Kruppel-Like Transcription Factors, Promoter Regions, Genetic, Protein Binding, Recombinant Proteins, Sequence Deletion, Signal Transduction, TCF Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques, Wnt Proteins, Zinc Fingers, beta Catenin
Cell Line, Cell Nucleus, Cyclin D, Cyclins, Humans, Kruppel-Like Transcription Factors, Promoter Regions, Genetic, Protein Binding, Recombinant Proteins, Sequence Deletion, Signal Transduction, TCF Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques, Wnt Proteins, Zinc Fingers, beta Catenin
FEBS Lett.
Date: Mar. 06, 2007
PubMed ID: 17289029
View in: Pubmed Google Scholar
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