Regulation of β-catenin transformation by the p300 transcriptional coactivator
| Autor: | Rashid Mosavin, Yongnian Sun, Eric R. Fearon, Frank T. Kolligs, Gary J. Nabel, Michael O. Hottiger |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Beta-catenin
Transcription Genetic Adenomatous polyposis coli Lymphoid Enhancer-Binding Factor 1 Recombinant Fusion Proteins TCF/LEF family Cell Line Transactivation Jurkat Cells Mice Tumor Cells Cultured Animals Humans Neoplastic transformation Enhancer Transcription factor beta Catenin Multidisciplinary biology Nuclear Proteins Biological Sciences Molecular biology Cell biology DNA-Binding Proteins Cytoskeletal Proteins Cell Transformation Neoplastic Gene Expression Regulation biology.protein Trans-Activators E1A-Associated p300 Protein Lymphoid enhancer-binding factor 1 Transcription Factors |
| Popis: | The β-catenin protein plays a critical role in embryonic development and mature tissue homeostasis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction. In colon and other cancers, mutations of β-catenin or the adenomatous polyposis coli (APC) tumor suppressor appear to stabilize β-catenin and enhance its interaction with T cell factor (TCF) or lymphoid enhancer factor (Lef) transcription factors. At present, a complete picture of the means by which β-catenin's interactions with TCF/Lef proteins contribute to neoplastic transformation is lacking. We report that the transcriptional coactivator p300 interacts with β-catenin in vitro and in vivo and is critical for β-catenin-mediated neoplastic transformation. p300 synergistically activates β-catenin/TCF transcription, and their biochemical association requires the CH1 domain of p300 and a region of β-catenin that includes its NH 2 -terminal transactivation domain and the first two armadillo repeats. Lowering of cellular p300 levels by using a ribozyme directed against p300 reduced TCF transcriptional activity and inhibited the neoplastic growth properties of a β-catenin-transformed rat epithelial cell line and a human colon carcinoma line with a β-catenin mutation. These findings demonstrate a critical role for p300 in β-catenin/TCF transcription and in cancers arising from defects in β-catenin regulation. |
| Databáze: | OpenAIRE |
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