Axin, an inhibitor of the Wnt signalling pathway, interacts with β‐catenin, GSK‐3β and APC and reduces the β‐catenin level

  title={Axin, an inhibitor of the Wnt signalling pathway, interacts with $\beta$‐catenin, GSK‐3$\beta$ and APC and reduces the $\beta$‐catenin level},
  author={T. Nakamura and Fumihiko Hamada and Takao Ishidate and Kanako Anai and Kohichi Kawahara and Kumao Toyoshima and Tetsu Akiyama},
  journal={Genes to Cells},
The Wnt/Wingless signalling pathway plays an important role in both embryonic development and tumorigenesis. β‐Catenin and Axin are positive and negative effectors of the Wnt signalling pathway, respectively. 
Reconstituting regulation of the canonical Wnt pathway by engineering a minimal β-catenin destruction machine
Essential components of APC and Axin required for their cooperative function are identified, and the data are used to design a minimal β-catenin–destruction machine.
Wnt/beta-catenin signaling.
  • T. Akiyama
  • Biology
    Cytokine & growth factor reviews
  • 2000
Mini Review Wnt/b-catenin signaling
The Wnt/Wingless signaling transduction pathway plays an important role in both embryonic development and tumorigenesis and mutations in APC or bcatenin have been found to be responsible for the genesis of human cancers.
Inhibition of Wnt signaling by ICAT, a novel β-catenin-interacting protein
It is suggested that ICAT negatively regulates Wnt signaling via inhibition of the interaction between β-catenin and TCF and is integral in development and cell proliferation.
Axin and hepatocellular carcinomas
A gene (AXIN1) encoding another component of the Wnt-signalling pathway is reported to be mutated in human tumours, underscoring the oncogenic consequences of inappropriate activation of
The links between axin and carcinogenesis
This review explores the intriguing connections between defects in axin function and human diseases and indicates that these molecules are the primary limiting components of this pathway.
Deconstructing the ßcatenin destruction complex: mechanistic roles for the tumor suppressor APC in regulating Wnt signaling
APC is a key tumor suppressor and Wnt signaling regulator, but its mechanism of action remains mysterious. We combined parallel assays in Drosophila and cultured human colon cancer cell lines to test
Interaction among Gsk-3, Gbp, Axin, and APC in Xenopus Axis Specification
GBP functions by preventing the GSK-3–mediated phosphorylation of a protein substrate without eliminating its catalytic activity, and it is shown that APC is impinging upon the canonical Wnt pathway in this model system.
Axin: A Master Scaffold for Multiple Signaling Pathways
The data are reviewed to show how Axin regulates multiple signaling pathways by serving as a scaffold protein, controlling diverse cellular functions in proliferation, fate determination, and suppression of tumorigenesis.
ING5 inhibits lung cancer invasion and epithelial–mesenchymal transition by inhibiting the WNT/β‐catenin pathway
This study has shown that ING5 overexpression inhibits lung cancer aggressiveness and epithelial–mesenchymal transition (EMT) with unknown mechanisms.


Bridging of β-catenin and glycogen synthase kinase-3β by Axin and inhibition of β-catenin-mediated transcription
It is shown that Axin simultaneously binds two components of the Wnt pathway, β-catenin and its negative regulator glycogen synthase kinase-3β, and can block signaling stimulated by Wnt or by adenomatous polyposis coli mutations.
Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.
Control of stability of beta-catenin is central in the wnt signaling pathway. Here, the protein conductin was found to form a complex with both beta-catenin and the tumor suppressor gene product
Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex Assembly
It is shown that when β-catenin is present in excess, APC binds to another component of the WINGLESS pathway, glycogen synthase kinase 3β (GSK3β), a mammalian homolog of Drosophila ZESTE WHITE 3, which was a good substrate for GSK3β in vitro and the phosphorylation sites were mapped to the central region of APC.
β‐catenin is a target for the ubiquitin–proteasome pathway
It is shown that ubiquitination of β‐catenin is greatly reduced in Wnt‐expressing cells, providing the first evidence that the ubiquitin–proteasome degradation pathway may act downstream of GSK3β in the regulation ofβ‐ catenin.
Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK‐3β and β‐catenin and promotes GSK‐3β‐dependent phosphorylation of β‐catenin
The results suggest that rAxin negatively regulates the Wnt signaling pathway by interacting with GSK‐3β and β‐catenin and mediating the signal from GSK•3β to β‐ catenin.
Cadherins and catenins in development.
Functional interaction of β-catenin with the transcription factor LEF-1
β-catenin regulates gene expression by direct interaction with transcription factors such as LEF-1, providing a molecular mechanism for the transmission of signals from cell-adhesion components or wnt protein to the nucleus.
Wingless inactivates glycogen synthase kinase‐3 via an intracellular signalling pathway which involves a protein kinase C.
Findings provide the first biochemical evidence in support of the genetically defined pathway from Wg to Zw3/Sgg, and suggest a previously uncharacterized role for a PKC upstream of GSK‐3/Zw3 during Wnt/Wg signal transduction.
DAP‐1, a novel protein that interacts with the guanylate kinase‐like domains of hDLG and PSD‐95
The human homologue of the Drosophila discs large tumour suppressor protein (hDLG) and closely related proteins such as postsynaptic density protein 95 kDa (PSD‐95) are associated with