Ginkgolic Acid Inhibits Protein SUMOylation by Blocking Formation of the E1-SUMO Intermediate
Ginkgolic Acid Inhibits Protein SUMOylation by Blocking Formation of the E1-SUMO Intermediate
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DOI：
10.1016/j.chembiol.2009.01.009
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发表时间：
2009-02-27
影响因子：
--
通讯作者：
Yoshida, Minoru
中科院分区：
文献类型：
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作者：
Fukuda, Isao;Ito, Akihiro;Yoshida, Minoru
由小泛素相关修饰蛋白(SUMO)修饰的蛋白质控制着多种细胞功能。SUMO化或去SUMO过程的失调与癌症和神经退行性疾病的发生有关。然而，到目前为止，还没有小分子抑制蛋白SUMO化的报道。在这里，我们报告了银杏酸及其类似物龙胆酸对糖基化的抑制作用。银杏酸和龙胆酸在体外和体内都抑制蛋白质的SUMO化，而不影响体内的泛素化。与荧光标记探针的结合分析表明，银杏酸直接与EL结合，并抑制E1-SUMO中间体的形成。这些研究不仅将为研究相扑结合在细胞中的各种途径中的作用提供有用的工具，而且也将为开发针对涉及异常SUMO化的疾病的药物提供基础。
Protein modification by small ubiquitin-related modifier proteins (SUMOs) controls diverse cellular functions. Dysregulation of SUMOylation or deSUMOylation processes has been implicated in the development of cancer and neurodegenerative diseases. However, no small-molecule inhibiting protein SUMOylation has been reported so far. Here, we report inhibition of SUMOylation by ginkgolic acid and its analog, anacardic acid. Ginkgolic acid and anacardic acid inhibit protein SUMOylation both in vitro and in vivo without affecting in vivo ubiquitination. Binding assays with a fluorescently labeled probe showed that ginkgolic acid directly binds El and inhibits the formation of the E1-SUMO intermediate. These studies will provide not only a useful tool for investigating the roles of SUMO conjugations in a variety of pathways in cells, but also a basis for the development of drugs targeted against diseases involving aberrant SUMOylation.