Tei Shuchin, Saitoh Noriko, Funahara Tetsushi, Iida Shin-ichi, Nakatsu Yuko, Kinoshita Kayo, Kinoshita Yoshikazu, Saya Hideyuki, Nakao Mitsuyoshi
Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo, Kumamoto, Japan.
J Cell Sci. 2009 Sep 1;122(Pt 17):3190-8. doi: 10.1242/jcs.049627. Epub 2009 Aug 11.
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.
多瘤病毒的大T抗原靶向控制基本过程的细胞蛋白，包括p53和肿瘤抑制因子RB家族。T抗原诱导细胞转化的机制需要全面研究，因为可能有尚未确定的靶蛋白参与这一过程。此外，最近发现的多瘤病毒与特定的人类疾病有关，如侵袭性皮肤癌。在这里，我们报告猿猴病毒40（SV40）大T抗原与转化酸性卷曲螺旋蛋白TACC2相互作用，TACC2参与有丝分裂中微管的稳定。T抗原直接结合TACC2并诱导微管功能障碍，导致有丝分裂纺锤体紊乱、有丝分裂进程缓慢和染色体错配。这些有丝分裂缺陷是由与TACC2相互作用最小的N端缺失的T抗原引起的，而TACC2的过表达抑制了T抗原诱导的微管去稳定化。因此，TACC2可能是T抗原在细胞转化起始过程中破坏微管调节和染色体遗传的关键靶点。
