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

Nakamura, Tsutomu; Hamada, Fumihiko; Ishidate, Takao; Anai, Ken-ichi; Kawahara, Kohichi; Toyoshima, Kumao; Akiyama, Tetsu

doi:10.1046/j.1365-2443.1998.00198.x

Cited by 284 publications

(220 citation statements)

References 46 publications

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“…Therefore, we investigated whether axin polymerization and puncta formation were required for assembly of the destruction complex, and whether they influence recruitment and b-catenin degradation. Previous studies have shown that the DIX domain is important for b-catenin regulation (Kishida et al, 1999;Sakanaka and Williams, 1999), however, it has also been reported that deletion of the DIX domain does not affect the ability of axin to alter b-catenin localization (Nakamura et al, 1998). We tested the ability of axinDDIX-RFP to recruit b-catenin in cells treated with proteasome inhibitors ( Figure 6).…”

Section: Resultsmentioning

confidence: 96%

Recruitment of adenomatous polyposis coli and β-catenin to axin-puncta

et al. 2008

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The adenomatous polyposis coli (APC) tumour suppressor is a multifunctional protein involved in the regulation of Wnt signalling and cytoskeletal dynamics. Little is known about how APC controls these disparate functions. In this study, we have used APC-and axin-fluorescent fusion proteins to examine the interactions between these proteins and show that the functionally distinct populations of APC are also spatially separate. Axin-RFP forms cytoplasmic punctate structures, similar to endogenous axin puncta. Axin-RFP recruits b-catenin destruction complex proteins, including APC, b-catenin, glycogen synthase kinase-3-b (GSK3-b) and casein kinase-1-a (CK1-a). Recruitment into axin-RFP puncta sequesters APC from clusters at cell extensions and this prevents its microtubule-associated functions. The interaction between APC-GFP and axin-RFP within the cytoplasmic puncta is direct and dramatically alters the dynamic properties of APC-GFP. However, recruitment of APC to axin puncta is not absolutely required for b-catenin degradation. Instead, formation of axin puncta, mediated by the DIX domain, is required for b-catenin degradation. An axinDDIX mutant did not form puncta, but still mediated recruitment of destruction complex proteins and phosphorylation of b-catenin. We conclude that there are distinct pools of APC and that the formation of axin puncta, rather than the axin/APC complex, is essential for b-catenin destruction.

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Section: Resultsmentioning

confidence: 96%

Recruitment of adenomatous polyposis coli and β-catenin to axin-puncta

et al. 2008

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“…The APC gene encodes a protein of 2843 amino acids that are associated with b-catenin, Axin and conductin/Axil (Rubinfeld et al, 1993;Behrens et al, 1998;Ikeda et al, 1998Nakamura et al, 1998;Yamamoto et al, 1998). These proteins are important components of the Wnt/ Wingless signal transduction pathway, which controls embryonic pattern formation (Nusse and Varmus, 1992;Cadigan and Nusse, 1997).…”

Section: Introductionmentioning

confidence: 99%

The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase

et al. 2000

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The adenomatous polyposis coli (APC) gene is mutated in familial adenomatous polyposis and in many sporadic colorectal tumors. The carboxyl-terminal S/TXV motif of the APC gene product interacts with the PDZ domain of hDLG, the human homolog of the Drosophila lethal (1) discs large-1 (dlg) tumor suppressor. In the present study, we found that overexpression of hDLG suppresses cell proliferation by blocking cell cycle progression from the G0/G1 to S phase. This inhibition of cell cycle progression was abolished when the PDZ, SH3 or guanylate kinase-like domain of hDLG was mutated. Moreover, overexpression of these mutant hDLGs partially interfered with the cell cycle blocking activity of APC. Consistent with this result, mutant APC lacking the S/TXV motif exhibited weaker cell cycle blocking activity than the intact APC. These results suggest that APC-hDLG complex formation plays an important role in transducing the APC cell cycle blocking signal.

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“…The product of AXIN1, a gene that was first isolated from the murine Fused locus as an inhibitor of Wnt signaling (Zeng et al 1997), was later shown to reduce -catenin by forming a complex with -catenin, GSK-3 (glycogen synthase kinase-3 ), and APC (adenomatous polyposis coli) (Kishida et al 1998, Nakamura et al 1998. By screening primary HCCs for mutations in the human homologue (AXIN1), we previously identified somatic mutations that all resulted in truncation of the predicted protein (Satoh et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Identification of novel polymorphisms in the AXIN1 and CDX-2 genes

et al. 2000

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Axin and Cdx-2 play important roles in the tumorigenesis of human liver and colon. We have identified seven novel single-nucleotide polymorphisms (SNPs) in the AXIN1 gene and three in the CDX-2 gene. The identification of SNPs in these cancer-associated genes establishes a basis for future investigations to detect losses of heterozygosity in tumors; these SNPs may also provide genetic background information associated with cancer risk.

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

Abstract: Background: The Wnt/Wingless signalling pathway plays an important role in both embryonic development and tumorigenesis. b-Catenin and Axin are positive and negative effectors of the Wnt signalling pathway, respectively.

Cited by 284 publications

References 46 publications

Recruitment of adenomatous polyposis coli and β-catenin to axin-puncta

Recruitment of adenomatous polyposis coli and β-catenin to axin-puncta

The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase

Identification of novel polymorphisms in the AXIN1 and CDX-2 genes

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