Department of Signal Transduction Sciences, Kagawa University, Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
FEBS Lett. 2010 Nov 19;584(22):4517-23. doi: 10.1016/j.febslet.2010.09.052. Epub 2010 Oct 21.
Although the precise intracellular roles of S100 proteins are not fully understood, these proteins are thought to be involved in Ca(2+)-dependent diverse signal transduction pathways. In this report, we identified importin α as a novel target of S100A6. Importin α contains armadillo repeats, essential for binding to nuclear localization signals. Based on the results from GST pull-down assay, gel-shift assay, and co-immunoprecipitation, we demonstrated that S100A6 specifically interacts with the armadillo repeats of importin α in a Ca(2+)-dependent manner, resulting in inhibition of the nuclear localization signal (NLS)-importin α complex formation in vitro and in vivo. These results indicate S100A6 may regulate the nuclear transport of NLS-cargos in response to increasing concentrations of intracellular Ca(2+).
虽然 S100 蛋白的确切细胞内作用尚未完全了解，但这些蛋白被认为参与 Ca(2+)-依赖性的多种信号转导途径。在本报告中，我们鉴定了 importin α 是 S100A6 的一个新的靶标。Importin α 含有对与核定位信号结合至关重要的 armadillo 重复序列。基于 GST 下拉测定、凝胶迁移率变动测定和共免疫沉淀的结果，我们证明 S100A6 以 Ca(2+)-依赖的方式特异性地与 importin α 的 armadillo 重复序列相互作用，导致体外和体内核定位信号（NLS）-importin α 复合物形成的抑制。这些结果表明 S100A6 可能会根据细胞内 Ca(2+)浓度的增加来调节 NLS-货物的核转运。
