| First Author | Amen M | Year | 2007 |
| Journal | Mol Cell Biol | Volume | 27 |
| Issue | 21 | Pages | 7560-73 |
| PubMed ID | 17785445 | Mgi Jnum | J:129071 |
| Mgi Id | MGI:3768606 | Doi | 10.1128/MCB.00315-07 |
| Citation | Amen M, et al. (2007) PITX2 and beta-catenin interactions regulate Lef-1 isoform expression. Mol Cell Biol 27(21):7560-73 |
| abstractText | Lef-1 and PITX2 function in the Wnt signaling pathway by recruiting and interacting with beta-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 beta-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 beta-catenin-dependent Lef-1 isoform (Lef-1 FL) while decreasing expression of the N-terminally truncated beta-catenin-independent isoform. Our research revealed a novel interaction between PITX2, Lef-1, and beta-catenin in which the Lef-1 beta-catenin binding domain 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. |
