Beardmore Victoria A, Ahonen Leena J, Gorbsky Gary J, Kallio Marko J
Department of Cell Biology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Oklahoma City, OK 73104, USA.
J Cell Sci. 2004 Aug 15;117(Pt 18):4033-42. doi: 10.1242/jcs.01242. Epub 2004 Jul 27.
The inhibitor of apoptosis protein survivin is implicated in two key biological events: in the control of cell proliferation and in the regulation of cell lifespan. Although the details of mitotic roles of survivin are unclear, the protein appears to modulate microtubule function and might participate in regulating the spindle checkpoint. Survivin physically associates with Aurora B, a serine-threonine kinase involved in microtubule attachment to centromeres and regulation of chromosome segregation. Here we have examined the dynamics and localization of a survivin-GFP chimera using high-resolution fluorescence microscopy and photobleaching. Survivin forms a bi-partite structure at the inner centromere that undergoes significant stretching during mitosis. Photobleaching experiments revealed marked changes in rates of survivin turnover at centromeres. These were regulated by stage of the cell cycle, microtubule attachment, and Aurora B kinase activity. We hypothesize that changes in the turnover of survivin at centromeres influence the stability of kinetochore-microtubule attachment and signaling of the spindle checkpoint.
凋亡抑制蛋白Survivin与两个关键生物学事件有关：控制细胞增殖和调节细胞寿命。尽管Survivin在有丝分裂中的具体作用细节尚不清楚，但该蛋白似乎可调节微管功能，并可能参与纺锤体检查点的调控。Survivin与Aurora B在物理上相互关联，Aurora B是一种丝氨酸 - 苏氨酸激酶，参与微管与着丝粒的附着以及染色体分离的调控。在此，我们使用高分辨率荧光显微镜和光漂白技术研究了Survivin - GFP嵌合体的动力学和定位。Survivin在着丝粒内部形成一种二分结构，在有丝分裂期间会发生显著拉伸。光漂白实验揭示了着丝粒处Survivin周转速率的显著变化。这些变化受细胞周期阶段、微管附着和Aurora B激酶活性的调节。我们推测，着丝粒处Survivin周转的变化会影响动粒 - 微管附着的稳定性和纺锤体检查点的信号传导。
