Abstract
β-Catenin is a biologically important molecule playing critical roles in both cell adhesion and transcriptional regulation in the Wnt pathway. Here, we show that phospho-β-catenin (phosphorylated at Ser33/37/Thr41), which is reported to be degraded immediately after its phosphorylation, accumulated in the centrosome. Whereas phospho-mimicking mutant, S33/37/T41E-β-catenin, could localize to the centrosome, S33A-β-catenin that lacks the phosphorylation site lost its localization to the centrosome. Phospho-β-catenin localized mainly to mother centrosome during the interphase and was recruited to daughter centrosome in M-phase. Depletion of β-catenin with small interfering RNA or inhibition of its phosphorylation by LiCl treatment caused disruption of radial microtubule (MT) array and retardation of the MT regrowth during the recovery from nocodazole treatment. In addition, these treatments increased the frequency of mono-astral MT reorganization. Furthermore, overexpression of the nonphosphorylatable β-catenin, but not the phospho-mimicking β-catenin, markedly disrupted radial MT array and repressed the MT regrowth. In contrast, phospho-mimicking β-catenin localized to both of the duplicated centrosomes with aberrant larger and denser radial MTs array formation. In addition, some of the cells overexpressing phospho-mimicking β-catenin had multiple centrosomes. Taken together, this study demonstrates a novel role of phospho-β-catenin in MT organization at the centrosomes.
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Abbreviations
- phospho-β-catenin:
-
phosphorylated β-catenin at serine33/37/threonine41
- GSK-3β:
-
Glycogen synthase kinase 3β
- MT:
-
microtubule
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Acknowledgements
We thank members and staffs of the Hamaguchi laboratory for their technical assistance and helpful discussion. This work was supported by a Grant-in-Aid for COE research from the Ministry of Education, Science, Culture and Technology, Japan.
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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).
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Huang, P., Senga, T. & Hamaguchi, M. A novel role of phospho-β-catenin in microtubule regrowth at centrosome. Oncogene 26, 4357–4371 (2007). https://doi.org/10.1038/sj.onc.1210217
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DOI: https://doi.org/10.1038/sj.onc.1210217
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