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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kimbrel, Erin A. Kung, Andrew L. |
| Description | Author Affiliation: Kimbrel EA ( Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.) |
| Abstract | Hyperactivated beta-catenin is a commonly found molecular abnormality in colon cancer, and its nuclear accumulation is thought to promote the expression of genes associated with cellular proliferation and transformation. The p300 transcriptional co-activator binds to beta-catenin and facilitates transcription by recruiting chromatin remodeling complexes and general transcriptional apparatus. We have found that beta-TrCp1/Fbw1a, a member of the Skp1/Cullin/Rbx1/F-box E3 ubiquitin ligase complex, binds directly to p300 and co-localizes with it to beta-catenin target gene promoters. Our data show that Fbw1a, which normally targets beta-catenin for degradation, works together with p300 to enhance the transcriptional activity of beta-catenin, whereas other F-box/WD40 proteins do not. Fbw1a also cooperates with p300 to co-activate transcription by SMAD3, another Fbw1a ubiquitylation target, but not p53 or HIF-1alpha, which are substrates for other ubiquitin ligase complexes. These results suggest that, although Fbw1a is part of a negative feedback loop for controlling beta-catenin levels in normal cells, its overexpression and binding to p300 may contribute to hyperactivated beta-catenin transcriptional activity in colon cancer cells. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 19 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-05-08 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | E1A-Associated P300 Protein Metabolism F-Box Proteins Transcription, Genetic Beta Catenin Genetics Beta-Transducin Repeat-Containing Proteins Amino Acid Sequence Blotting, Western Cells, Cultured Chromatin Immunoprecipitation Immunoprecipitation Luciferases Molecular Sequence Data Peptide Library Promoter Regions, Genetic Sequence Homology, Amino Acid Transcriptional Activation Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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