| http://purl.uniprot.org/citations/18339854 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18339854 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in beta-catenin or other Wnt pathway components that cause beta-catenin accumulation occur rarely in breast cancer. However, there is some evidence of beta-catenin protein accumulation in a subset of breast tumors. We have recently shown that Rad6B, an ubiquitin-conjugating enzyme, is a transcriptional target of beta-catenin/TCF. Here, we show that forced Rad6B overexpression in MCF10A breast cells induces beta-catenin accumulation, which despite being ubiquitinated is stable and transcriptionally active. A similar relationship between Rad6B, beta-catenin ubiquitination, and transcriptional activity was found in WS-15 and MDA-MB-231 breast cancer cells, and mouse mammary tumor virus-Wnt-1 mammary tumor-derived cells, implicating Rad6B in physiologic regulation of beta-catenin stability and activity. Ubiquitinated beta-catenin was detectable in chromatin immunoprecipitations performed with beta-catenin antibody in MDA-MB-231 but not MCF10A cells. Rad6B silencing caused suppression of beta-catenin monoubiquitination and polyubiquitination, and transcriptional activity. These effects were accompanied by a reduction in intracellular beta-catenin but with minimal effects on cell membrane-associated beta-catenin. Measurement of beta-catenin protein stability by cycloheximide treatment showed that Rad6B silencing specifically decreases the stability of high molecular beta-catenin with minimal effect upon the 90-kDa nascent form. In vitro ubiquitination assays confirmed that Rad6B mediates beta-catenin polyubiquitination, and ubiquitin chain extensions involve lysine 63 residues that are insensitive to 26S proteasome. These findings, combined with our previous data that Rad6B is a transcriptional target of beta-catenin, reveal a positive regulatory feedback loop between Rad6B and beta-catenin and a novel mechanism of beta-catenin stabilization/activation in breast cancer cells."xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-07-2111"xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/author | "Gerard B."xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/author | "Williams B.O."xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/author | "Tait L."xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/author | "Pauley R.J."xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/author | "Shekhar M.P."xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/pages | "1741-1750"xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/title | "Rad6B is a positive regulator of beta-catenin stabilization."xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://purl.uniprot.org/core/volume | "68"xsd:string |
| http://purl.uniprot.org/citations/18339854 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18339854 |
| http://purl.uniprot.org/citations/18339854 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18339854 |
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| http://purl.uniprot.org/uniprot/P63146#attribution-C0C9D608F15D462044D39032EF8BE98B | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/18339854 |
| http://purl.uniprot.org/uniprot/P63147#attribution-C0C9D608F15D462044D39032EF8BE98B | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/18339854 |
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| http://purl.uniprot.org/uniprot/#_P63147-mappedCitation-18339854 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18339854 |
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| http://purl.uniprot.org/uniprot/P63146 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18339854 |
| http://purl.uniprot.org/uniprot/P63147 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18339854 |