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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 6
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pubmed:dateCreated |
2005-3-14
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pubmed:abstractText |
PITX2, beta-catenin and lymphoid enhancer factor (LEF-1) are required for the inductive formation of several epithelial-derived organs, including teeth. Lef-1 is expressed in the dental epithelium after Pitx2, and both factors have overlapping expression patterns in the tooth bud and cap stages. Our analysis of Pitx2-/- mutant mice showed reduced Lef-1 expression in facial tissues by RT-PCR and quantitative RT-PCR. Consistent with these results we show that the human 2.5 kb LEF-1 promoter is activated by PITX2. Furthermore, the LEF-1 promoter is differentially activated by PITX2 isoforms, which are co-expressed in dental epithelium. The 2.5 kb LEF-1 promoter contains two regions that act to inhibit its transcription in concert with PITX2. The proximal region contains a Wnt-responsive element (WRE) that attenuates PITX2 activation. LEF-1 cannot autoregulate LEF-1 expression; however co-transfection of PITX2 and LEF-1 result in a synergistic activation of the 2.5 kb LEF-1 promoter. LEF-1 specifically interacts with the PITX2 C-terminal tail. Deletion of a distal 800 bp segment of the LEF-1 promoter resulted in enhanced PITX2 activation, and increased synergistic activation in the presence of LEF-1. Furthermore, beta-catenin in combination with PITX2 synergistically activates the LEF-1 promoter and this activation is independent of the Wnt-responsive element. beta-catenin directly interacts with PITX2 to synergistically regulate LEF-1 expression. We show a new mechanism where LEF-1 expression is regulated through PITX2, LEF-1 and beta-catenin direct physical interactions. LEF-1 and beta-catenin interactions with PITX2 provide new mechanisms for the regulation of PITX2 transcriptional activity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/LEF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Lef1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphoid Enhancer-Binding Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase,
http://linkedlifedata.com/resource/pubmed/chemical/homeobox protein PITX2
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9533
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1129-37
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15728254-Animals,
pubmed-meshheading:15728254-Blotting, Western,
pubmed-meshheading:15728254-Cricetinae,
pubmed-meshheading:15728254-Cytoskeletal Proteins,
pubmed-meshheading:15728254-DNA, Complementary,
pubmed-meshheading:15728254-DNA-Binding Proteins,
pubmed-meshheading:15728254-Epithelium,
pubmed-meshheading:15728254-Gene Deletion,
pubmed-meshheading:15728254-Gene Expression Regulation,
pubmed-meshheading:15728254-Glutathione Transferase,
pubmed-meshheading:15728254-Homeodomain Proteins,
pubmed-meshheading:15728254-Humans,
pubmed-meshheading:15728254-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:15728254-Luciferases,
pubmed-meshheading:15728254-Lymphoid Enhancer-Binding Factor 1,
pubmed-meshheading:15728254-Mice,
pubmed-meshheading:15728254-Mice, Transgenic,
pubmed-meshheading:15728254-Models, Genetic,
pubmed-meshheading:15728254-Plasmids,
pubmed-meshheading:15728254-Promoter Regions, Genetic,
pubmed-meshheading:15728254-Protein Binding,
pubmed-meshheading:15728254-Protein Isoforms,
pubmed-meshheading:15728254-Protein Structure, Tertiary,
pubmed-meshheading:15728254-Recombinant Fusion Proteins,
pubmed-meshheading:15728254-Response Elements,
pubmed-meshheading:15728254-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15728254-Trans-Activators,
pubmed-meshheading:15728254-Transcription, Genetic,
pubmed-meshheading:15728254-Transcription Factors,
pubmed-meshheading:15728254-Transcriptional Activation,
pubmed-meshheading:15728254-Transfection,
pubmed-meshheading:15728254-Wnt Proteins,
pubmed-meshheading:15728254-beta Catenin,
pubmed-meshheading:15728254-beta-Galactosidase
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pubmed:year |
2005
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pubmed:articleTitle |
PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter.
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pubmed:affiliation |
Department of Biological Science, The University of Tulsa, 600 S College Ave., Tulsa, OK 74104-3189, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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