Abstract
Wnt Signaling Regulates Lymphoid Enhancer Factor (Lef‐1) Isoform Expression Through Functional Interactions Between PITX2, beta‐catenin and Lef‐1
The FASEB journal, Vol.21(5), pp.A656-A656
04/2007
DOI: 10.1096/fasebj.21.5.A656
Abstract
Lef‐1 and PITX2 function in the Wnt signaling pathway by recruiting and interacting with beta‐catenin to activate target genes. PITX2 enhances expression of the full‐length beta‐catenin‐dependent Lef‐1 isoform (Lef‐1 FL), while decreasing expression of the N‐terminal truncated beta‐catenin‐independent isoform. Transgenic mice expressing LacZ driven by the 2.5kb LEF‐1 promoter demonstrated expression in the tooth epithelium, and correlated with endogenous Lef‐1 FL epithelial expression. Chromatin immunoprecipitation (ChIP) assays confirmed the Lef‐1 promoter as a PITX2 downstream target. PITX2 isoforms differentially regulate the LEF‐1 promoter, and beta‐catenin synergistically enhanced activation of the LEF‐1 promoter in combination with PITX2 and either Lef‐1 isoform. Our research reveals a novel interaction between PITX2, Lef‐1 and beta‐catenin, in which the Lef‐1 beta‐catenin binding domain (bBD) is dispensable for its interaction with PITX2. PITX2 interacts with two sites within the Lef‐1 protein. Furthermore, beta‐catenin interacts with the PITX2 homeodomain and Lef‐1 interacts with the PITX2 C‐terminal tail. Lef‐1 and beta‐catenin interact simultaneously and independently with PITX2 through two different sites to regulate PITX2 transcriptional activity. These data support a role for PITX2 in cell proliferation, migration and cell division through differential Lef‐1 isoform expression and interactions with Lef‐1 and beta‐catenin.
Details
- Title: Subtitle
- Wnt Signaling Regulates Lymphoid Enhancer Factor (Lef‐1) Isoform Expression Through Functional Interactions Between PITX2, beta‐catenin and Lef‐1
- Creators
- Brad A Amendt - Texas A&M Health Science CenterXiaoming Liu - University of IowaMelanie Amen - Texas A&M Health Science CenterJohn F Engelhardt - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.21(5), pp.A656-A656
- DOI
- 10.1096/fasebj.21.5.A656
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Publisher
- Federation of American Societies for Experimental Biology
- Number of pages
- 1
- Language
- English
- Date published
- 04/2007
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthodontics; Anatomy and Cell Biology; Radiation Oncology; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
- Record Identifier
- 9984288760002771
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