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Spindle checkpoint protein Bub1 corrects mitotic aberrancy induced by human T-cell leukemia virus type I Tax

Oncogene volume 25, pages 3621–3627 (2006)Cite this article

Abstract

Bub1 is a component of the mitotic spindle checkpoint apparatus. Abnormality of this apparatus is known to cause multinuclei formation, a hallmark of chromosomal instability (CIN). A549, aneuploid cell line, aberrantly passed through the mitotic phase and became multinuclei morphology in the presence of nocodazole. Time-lapse videomicroscopy showed unreported bizarre morphology, which we named ‘mitotic lobulation’ in A549 cells just before the exit from mitosis and multinuclei formation. External expression of wild-type Bub1-EGFP clearly suppressed the multinuclei formation by retaining A549 cells at the mitotic phase during 48 h of time-lapse observation. This suppressive effect on mitotic aberrancy should not be mere restoration of normal Bub1 function, because A549 cells express proper amount of Bub1, which distributed cytoplasm during interphase and concentrated at kinetochore in metaphase. Furthermore, external expression of wild-type Bub1-EGFP suppressed multinuclei formation induced by Tax both in A549 and HeLa cells. Tax is known to induce mitotic abnormality by binding and inactivating Mad1. These observations, therefore, suggest functional redundancy between Bub1 and other mitotic checkpoint protein(s) and a possibility of correction of mitotic aberrancy by external Bub1 expression.

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Acknowledgements

We thank Dr Hatanaka M (Shionogi pharmaceuticals) for providing Tax plasmid, pH2R40M, and Dr Lengauer (Johns Hopkins University School of Medicine) for providing Bub1wt and Bub1v429 cDNA, respectively. We also thank Sakura-eigasha for technical assistance. Confocal microscopy was performed at Juntendo University Research Institute for Disease of Old Ages.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan

    M Sasaki, K Sugimoto, K Tamayose, M Ando & K Oshimi

  2. Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan

    Y Tanaka

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  1. M Sasaki
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Correspondence to K Sugimoto.

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Sasaki, M., Sugimoto, K., Tamayose, K. et al. Spindle checkpoint protein Bub1 corrects mitotic aberrancy induced by human T-cell leukemia virus type I Tax. Oncogene 25, 3621–3627 (2006). https://doi.org/10.1038/sj.onc.1209404

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