Journal article
PITX2 and β-Catenin Interactions Regulate Lef-1 Isoform Expression
Molecular and cellular biology, Vol.27(21), pp.7560-7573
11/2007
DOI: 10.1128/MCB.00315-07
PMCID: PMC2169058
PMID: 17785445
Abstract
ABSTRACT
Lef-1 and PITX2 function in the Wnt signaling pathway by recruiting and interacting with β-catenin to activate target genes. Chromatin immunoprecipitation (ChIP) assays identified the
Lef-1
promoter as a PITX2 downstream target. Transgenic mice expressing
LacZ
driven by the 2.5-kb
LEF-1
promoter demonstrated expression in the tooth epithelium correlated with endogenous
Lef-1 FL
epithelial expression. PITX2 isoforms regulate the
LEF-1
promoter, and β-catenin synergistically enhanced activation of the
LEF-1
promoter in combination with PITX2 and Lef-1 isoforms. PITX2 enhances endogenous expression of the full-length β-catenin-dependent Lef-1 isoform (Lef-1 FL) while decreasing expression of the N-terminally truncated β-catenin-independent isoform. Our research revealed a novel interaction between PITX2, Lef-1, and β-catenin in which the Lef-1 β-catenin binding domain is dispensable for its interaction with PITX2. PITX2 interacts with two sites within the Lef-1 protein. Furthermore, β-catenin interacts with the PITX2 homeodomain and Lef-1 interacts with the PITX2 C-terminal tail. Lef-1 and β-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 β-catenin.
Details
- Title: Subtitle
- PITX2 and β-Catenin Interactions Regulate Lef-1 Isoform Expression
- Creators
- Melanie Amen - Texas A&M Health Science CenterXiaoming Liu - University of IowaUsha Vadlamudi - University of TulsaGabriela Elizondo - Tecnológico de MonterreyEvan Diamond - Texas A&M Health Science CenterJohn F. Engelhardt - University of IowaBrad A. Amendt - Texas A&M Health Science Center
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.27(21), pp.7560-7573
- DOI
- 10.1128/MCB.00315-07
- PMID
- 17785445
- PMCID
- PMC2169058
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 11/2007
- 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
- 9984284346902771
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