MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway
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Ser Sue Ng
Abstract
A central point of regulation in the Wnt/β-catenin signalling pathway is the formation of the β-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 β-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/β-catenin pathway. These results suggest that MAP3K1, previously reported as an Axin1 inter-actor in c-Jun NH2-terminal kinase pathway, is also involved in the canonical Wnt signalling pathway and positively regulates expression of Wnt target genes.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- EDITORIAL
- Highlight: Signal Transduction and Disease
- HIGHLIGHT: SIGNAL TRANSDUCTION AND DISEASE
- Phosphorylase and the origin of reversible protein phosphorylation
- β-Catenin as a multilayer modulator of zonal cytochrome P450 expression in mouse liver
- Glycome profiling using modern glycomics technology: technical aspects and applications
- Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity
- MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway
- Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function
- GENES AND NUCLEIC ACIDS
- 6S RNA-dependent inhibition of RNA polymerase is released by RNA-dependent synthesis of small de novo products
- PROTEIN STRUCTURE AND FUNCTION
- Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation
- Peptides from the Mycobacterium tuberculosis Rv1980c protein involved in human cell infection: insights into new synthetic subunit vaccine candidates
- The epimerase activity of anthocyanidin reductase from Vitis vinifera and its regiospecific hydride transfers
- Antibacterial activity of radical scavengers against class Ib ribonucleotide reductase from Bacillus anthracis
- CELL BIOLOGY AND SIGNALING
- Signal transduction in CHO cells stably transfected with domain-selective forms of murine ACE
- The impact of methylmercury on 1,25-dihydroxyvitamin D3-induced transcriptomic responses in dolphin skin cells
- PROTEOLYSIS
- An examination of the proteolytic activity for bovine pregnancy-associated glycoproteins 2 and 12
- Analysis of an autoproteolytic activity of rice yellow mottle virus silencing suppressor P1
- Identification of novel peptide inhibitors for human trypsins
