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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
40
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pubmed:dateCreated |
2003-9-29
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pubmed:abstractText |
Wnt signaling is essential during development while deregulation of this pathway frequently leads to the formation of various tumors including colorectal carcinomas. A key component of the pathway is beta-catenin that, in association with TCF-4, directly regulates the expression of Wnt-responsive genes. To identify novel binding partners of beta-catenin that may control its transcriptional activity, we performed a mammalian two-hybrid screen and isolated the Tax-interacting protein (TIP-1). The in vivo complex formation between beta-catenin and TIP-1 was verified by coimmunoprecipitation, and a direct physical association was revealed by glutathione S-transferase pull-down experiments in vitro. By using a panel of deletion mutants of both proteins, we demonstrate that the interaction is mediated by the PDZ (PSD-95/DLG/ZO-1 homology) domain of TIP-1 and requires primarily the last four amino acids of beta-catenin. TIP-1 overexpression resulted in a dose-dependent decrease in the transcriptional activity of beta-catenin when tested on the TOP/FOPFLASH reporter system. Conversely, siRNA-mediated knock-down of endogenous TIP-1 slightly increased endogenous beta-catenin transactivation function. Moreover, we show that overexpression of TIP-1 reduced the proliferation and anchorage-independent growth of colorectal cancer cells. These data suggest that TIP-1 may represent a novel regulatory element in the Wnt/beta-catenin signaling pathway.
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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/Agar,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/TAX1BP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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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 |
3
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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 |
38758-64
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pubmed:dateRevised |
2010-5-26
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pubmed:meshHeading |
pubmed-meshheading:12874278-Agar,
pubmed-meshheading:12874278-Animals,
pubmed-meshheading:12874278-Blotting, Western,
pubmed-meshheading:12874278-CHO Cells,
pubmed-meshheading:12874278-Carrier Proteins,
pubmed-meshheading:12874278-Cell Division,
pubmed-meshheading:12874278-Cell Line,
pubmed-meshheading:12874278-Colorectal Neoplasms,
pubmed-meshheading:12874278-Cricetinae,
pubmed-meshheading:12874278-Cytoskeletal Proteins,
pubmed-meshheading:12874278-Dose-Response Relationship, Drug,
pubmed-meshheading:12874278-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:12874278-Genes, Reporter,
pubmed-meshheading:12874278-Glutaminase,
pubmed-meshheading:12874278-Glutathione Transferase,
pubmed-meshheading:12874278-Humans,
pubmed-meshheading:12874278-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12874278-Luciferases,
pubmed-meshheading:12874278-Mice,
pubmed-meshheading:12874278-Microscopy, Fluorescence,
pubmed-meshheading:12874278-Models, Genetic,
pubmed-meshheading:12874278-Precipitin Tests,
pubmed-meshheading:12874278-Protein Binding,
pubmed-meshheading:12874278-Protein Structure, Tertiary,
pubmed-meshheading:12874278-Proteins,
pubmed-meshheading:12874278-RNA, Small Interfering,
pubmed-meshheading:12874278-RNA Interference,
pubmed-meshheading:12874278-Signal Transduction,
pubmed-meshheading:12874278-Trans-Activators,
pubmed-meshheading:12874278-Transcription, Genetic,
pubmed-meshheading:12874278-Transcriptional Activation,
pubmed-meshheading:12874278-Transfection,
pubmed-meshheading:12874278-Two-Hybrid System Techniques,
pubmed-meshheading:12874278-beta Catenin
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pubmed:year |
2003
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pubmed:articleTitle |
The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.
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pubmed:affiliation |
Laboratory for Genome Exploration Research Group, RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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