Shu Wenxiu, Chen Yan, Wu Qing, Li Rui, Cui Guohui
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Biol Pharm Bull. 2008 Jan;31(1):27-32. doi: 10.1248/bpb.31.27.
Since the first report about cytoplasmic nucleophosmin (NPM) in acute myelogenous leukemia with a normal karyotype was announced, the shuttling activity of NPM and its proper subcellular localization have drawn many attentions. Mechanisms that regulate nucleocytoplasmic transport of proteins may provide novel opportunities for drug development. Here we show that, in Jurkat cells, strong fluorescence density of NPM prevails in the nucleus, while, some key nucleoporins: Nup88 and Nup214 localize mainly in the cytoplasm. Deguelin, a natural occurring rotenoid, presents powerful anti-leukemia effects through proliferation inhibition and apoptosis induction in Jurkat cells. Deguelin downregulates the expression of NPM, Nup88 and Nup214 in a dose-dependent manner and reverts the localization of Nup88 and Nup214 to nuclear rim. These results suggest that deguelin exhibit its strong anti-leukemia effects might through the regulation of some nucleoporins, thus influence the subsequent abnormal expressions or localizations of some key proteins involved in proliferation and/or apoptosis, such as: NPM.
自从首次报道核型正常的急性髓系白血病中存在细胞质核磷蛋白(NPM)以来,NPM的穿梭活性及其正确的亚细胞定位引起了广泛关注。调节蛋白质核质转运的机制可能为药物开发提供新的机会。在这里,我们发现,在Jurkat细胞中,NPM的强荧光密度主要存在于细胞核中,而一些关键的核孔蛋白:Nup88和Nup214主要定位于细胞质中。鱼藤素是一种天然存在的鱼藤酮类化合物,通过抑制Jurkat细胞增殖和诱导凋亡呈现强大的抗白血病作用。鱼藤素以剂量依赖的方式下调NPM、Nup88和Nup214的表达,并使Nup88和Nup214的定位恢复到核边缘。这些结果表明,鱼藤素可能通过调节一些核孔蛋白发挥其强大的抗白血病作用,从而影响随后参与增殖和/或凋亡的一些关键蛋白的异常表达或定位,如NPM。