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First published online 11 August 2009
doi: 10.1242/jcs.049627

Journal of Cell Science 122, 3190-3198 (2009)
Published by The Company of Biologists 2009
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Research Article

Simian virus 40 large T antigen targets the microtubule-stabilizing protein TACC2

Shuchin Tei1,2, Noriko Saitoh1, Tetsushi Funahara1, Shin-ichi Iida3, Yuko Nakatsu1, Kayo Kinoshita1, Yoshikazu Kinoshita2, Hideyuki Saya3 and Mitsuyoshi Nakao1,*

1 Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
2 Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan
3 Division of Gene Regulation, Institute for Advanced Medical Research, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan

* Author for correspondence (mnakao{at}gpo.kumamoto-u.ac.jp)

Accepted 15 June 2009

The large T antigens of polyomaviruses target cellular proteins that control fundamental processes, including p53 and the RB family of tumor suppressors. Mechanisms that underlie T-antigen-induced cell transformation need to be fully addressed, because as-yet unidentified target proteins might be involved in the process. In addition, recently identified polyomaviruses are associated with particular human diseases such as aggressive skin cancers. Here, we report that simian virus 40 (SV40) large T antigen interacts with the transforming acidic coiled-coil-containing protein TACC2, which is involved in stabilizing microtubules in mitosis. T antigen directly binds TACC2 and induces microtubule dysfunction, leading to disorganized mitotic spindles, slow progression of mitosis and chromosome missegregation. These mitotic defects are caused by N-terminal-deleted T antigen, which minimally interacts with TACC2, whereas T-antigen-induced microtubule destabilization is suppressed by overexpressing TACC2. Thus, TACC2 might be a key target of T antigen to disrupt microtubule regulation and chromosomal inheritance in the initiation of cell transformation.

Key words: Large T antigen, TACC2, Chromosomes, Nucleus, Mitosis


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© The Company of Biologists Ltd 2009