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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
33
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pubmed:dateCreated |
2003-8-11
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pubmed:abstractText |
T cell factor (Tcf) proteins bind beta-catenin and are downstream effectors of Wnt/beta-catenin signals. A recently demonstrated interaction between beta-catenin and the androgen receptor (AR) ligand binding domain has suggested that AR may be a Tcf-independent Wnt/beta-catenin effector. This study demonstrates that there is a direct interaction between the AR DNA binding domain (DBD) and Tcf4. Tcf4 bound specifically to a glutathione S-transferase-ARDBD fusion protein and could be coimmunoprecipitated with beta-catenin and transfected AR or endogenous AR in prostate cancer cells. Transfected Tcf4 repressed the transcriptional activity of full-length AR and a VP16-ARDBD fusion protein, and this repression was only partially reversed by transfected beta-catenin. AR activation by cyproterone acetate, a partial agonist that did not support beta-catenin binding to the AR, was also repressed by Tcf4, further indicating that repression was not due to beta-catenin sequestration. Tcf4 could recruit beta-catenin to the AR DBD in vitro and to the cyproterone acetate-liganded AR in vivo. Chromatin immunoprecipitation experiments in LNCaP prostate cancer cells showed that endogenous AR was bound to a Tcf4-responsive element in the c-myc promoter. These findings indicate that AR and Tcf4 can interact directly and that this interaction may occur on the promoters or enhancers of particular genes. The direct AR-Tcf4 interaction, in conjunction AR- and Tcf4-beta-catenin binding, provides a mechanism for cooperative and selective gene regulation by AR and the Wnt/beta-catenin-Tcf pathway that may contribute to normal and neoplastic prostate growth.
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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/Androgen Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyproterone Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Androgen,
http://linkedlifedata.com/resource/pubmed/chemical/TCF Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/TCF7L2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor 7-Like 2...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Zebrafish Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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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 |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30828-34
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12799378-Androgen Antagonists,
pubmed-meshheading:12799378-Cyproterone Acetate,
pubmed-meshheading:12799378-Cytoskeletal Proteins,
pubmed-meshheading:12799378-Humans,
pubmed-meshheading:12799378-Ligands,
pubmed-meshheading:12799378-Male,
pubmed-meshheading:12799378-Prostatic Neoplasms,
pubmed-meshheading:12799378-Protein Binding,
pubmed-meshheading:12799378-Proto-Oncogene Proteins,
pubmed-meshheading:12799378-Receptors, Androgen,
pubmed-meshheading:12799378-Signal Transduction,
pubmed-meshheading:12799378-TCF Transcription Factors,
pubmed-meshheading:12799378-Trans-Activators,
pubmed-meshheading:12799378-Transcription Factor 7-Like 2 Protein,
pubmed-meshheading:12799378-Transcription Factors,
pubmed-meshheading:12799378-Transcriptional Activation,
pubmed-meshheading:12799378-Transfection,
pubmed-meshheading:12799378-Tumor Cells, Cultured,
pubmed-meshheading:12799378-Wnt Proteins,
pubmed-meshheading:12799378-Zebrafish Proteins,
pubmed-meshheading:12799378-beta Catenin
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pubmed:year |
2003
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pubmed:articleTitle |
A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4.
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pubmed:affiliation |
Cancer Biology Program, Hematology-Oncology Division, the Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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