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

Oncogene volume 27, pages 5808–5820 (2008)Cite this article

Abstract

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 β-catenin destruction complex proteins, including APC, β-catenin, glycogen synthase kinase-3-β (GSK3-β) and casein kinase-1-α (CK1-α). 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 β-catenin degradation. Instead, formation of axin puncta, mediated by the DIX domain, is required for β-catenin degradation. An axinΔDIX mutant did not form puncta, but still mediated recruitment of destruction complex proteins and phosphorylation of β-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 β-catenin destruction.

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Acknowledgements

We thank Dr M Prescott, Dr F Costantini and Dr D Capelluto for cDNA constructs. MCF, MJL and AWB are supported by NH&MRC program grant 234703; AHAC is an NH&MRC RD Wright Research Fellow.

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  1. Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Parkville, Victoria, Australia

    M C Faux, J L Coates, B Catimel, S Cody, A H A Clayton, M J Layton & A W Burgess

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  1. M C Faux
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  2. J L Coates
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Correspondence to M C Faux.

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Faux, M., Coates, J., Catimel, B. et al. Recruitment of adenomatous polyposis coli and β-catenin to axin-puncta. Oncogene 27, 5808–5820 (2008). https://doi.org/10.1038/onc.2008.205

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