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| pubmed-article:20128690 | lifeskim:mentions | umls-concept:C1332125 | lld:lifeskim |
| pubmed-article:20128690 | lifeskim:mentions | umls-concept:C1367675 | lld:lifeskim |
| pubmed-article:20128690 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:20128690 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:20128690 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:20128690 | pubmed:issue | 2-3 | lld:pubmed |
| pubmed-article:20128690 | pubmed:dateCreated | 2010-3-4 | lld:pubmed |
| pubmed-article:20128690 | pubmed:abstractText | A central point of regulation in the Wnt/beta-catenin signalling pathway is the formation of the beta-catenin destruction complex. Axin1, an essential negative regulator of Wnt signalling, serves as a scaffold within this complex and is critical for rapid turnover of beta-catenin. To examine the mechanism by which Wnt signalling disables the destruction complex, we used an immunoprecipitation-coupled proteomics approach to identify novel endogenous binding partners of Axin1. We found mitogen-activated protein kinase kinase kinase 1 (MAP3K1) as an Axin1 interactor in Ls174T colorectal cancer (CRC) cells. Importantly, confirmation of this interaction in HEK293T cells indicated that the Axin1-MAP3K1 interaction is induced and modulated by Wnt stimulation. siRNA depletion of MAP3K1 specifically abrogated TCF/LEF-driven transcription and Wnt3A-driven endogenous gene expression in both HEK293T as well as DLD-1 CRC. Expression of ubiquitin ligase mutants of MAP3K1 abrogated TCF/LEF transcription, whereas kinase mutants had no effect in TCF-driven activity, highlighting the essential role of the MAP3K1 E3 ubiquitin ligase activity in regulation of the Wnt/beta-catenin pathway. These results suggest that MAP3K1, previously reported as an Axin1 inter-actor in c-Jun NH(2)-terminal kinase pathway, is also involved in the canonical Wnt signalling pathway and positively regulates expression of Wnt target genes. | lld:pubmed |
| pubmed-article:20128690 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:20128690 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:20128690 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20128690 | pubmed:issn | 1437-4315 | lld:pubmed |
| pubmed-article:20128690 | pubmed:author | pubmed-author:CleversHansH | lld:pubmed |
| pubmed-article:20128690 | pubmed:author | pubmed-author:MahmoudiTokam... | lld:pubmed |
| pubmed-article:20128690 | pubmed:author | pubmed-author:HatzisPanteli... | lld:pubmed |
| pubmed-article:20128690 | pubmed:author | pubmed-author:MohammedShaba... | lld:pubmed |
| pubmed-article:20128690 | pubmed:author | pubmed-author:BoersemaPaul... | lld:pubmed |
| pubmed-article:20128690 | pubmed:author | pubmed-author:HeckAlbert... | lld:pubmed |
| pubmed-article:20128690 | pubmed:author | pubmed-author:LiVivian S... | lld:pubmed |
| pubmed-article:20128690 | pubmed:author | pubmed-author:Sue NgSerS | lld:pubmed |
| pubmed-article:20128690 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20128690 | pubmed:volume | 391 | lld:pubmed |
| pubmed-article:20128690 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20128690 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20128690 | pubmed:pagination | 171-80 | lld:pubmed |
| pubmed-article:20128690 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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| pubmed-article:20128690 | pubmed:articleTitle | MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway. | lld:pubmed |
| pubmed-article:20128690 | pubmed:affiliation | Hubrecht Institute, KNAW and University Medical Centre Utrecht, Uppsalalaan 8, NL-3584 CT Utrecht, The Netherlands. | lld:pubmed |
| pubmed-article:20128690 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20128690 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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