Linked Life Data

20128690

Source:http://linkedlifedata.com/resource/pubmed/id/20128690

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2010-3-4
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1437-4315
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
391
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
171-80
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20128690-Amino Acid Sequence, pubmed-meshheading:20128690-Axin Protein, pubmed-meshheading:20128690-Cell Line, pubmed-meshheading:20128690-Cell Line, Tumor, pubmed-meshheading:20128690-Humans, pubmed-meshheading:20128690-Immunoprecipitation, pubmed-meshheading:20128690-MAP Kinase Kinase Kinase 1, pubmed-meshheading:20128690-Molecular Sequence Data, pubmed-meshheading:20128690-Mutagenesis, Site-Directed, pubmed-meshheading:20128690-Protein Binding, pubmed-meshheading:20128690-RNA, Small Interfering, pubmed-meshheading:20128690-Repressor Proteins, pubmed-meshheading:20128690-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20128690-Signal Transduction, pubmed-meshheading:20128690-Transcription, Genetic, pubmed-meshheading:20128690-Wnt Proteins, pubmed-meshheading:20128690-beta Catenin
pubmed:articleTitle
MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway.
pubmed:affiliation
Hubrecht Institute, KNAW and University Medical Centre Utrecht, Uppsalalaan 8, NL-3584 CT Utrecht, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't