银杏酸通过阻断E1-小泛素样修饰蛋白（SUMO）中间体的形成来抑制蛋白质的SUMO化。

Ginkgolic acid inhibits protein SUMOylation by blocking formation of the E1-SUMO intermediate.

作者信息

Fukuda Isao, Ito Akihiro, Hirai Go, Nishimura Shinichi, Kawasaki Hisashi, Saitoh Hisato, Kimura Ken-Ichi, Sodeoka Mikiko, Yoshida Minoru

机构信息

Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.

出版信息

Chem Biol. 2009 Feb 27;16(2):133-40. doi: 10.1016/j.chembiol.2009.01.009.

DOI:10.1016/j.chembiol.2009.01.009

PMID:19246003

Abstract

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 E1 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.

摘要

小泛素相关修饰蛋白（SUMO）介导的蛋白质修饰调控多种细胞功能。SUMO化或去SUMO化过程的失调与癌症和神经退行性疾病的发生发展有关。然而，迄今为止尚未报道有小分子抑制蛋白质SUMO化。在此，我们报道了银杏酸及其类似物漆树酸对SUMO化的抑制作用。银杏酸和漆树酸在体外和体内均能抑制蛋白质SUMO化，且不影响体内泛素化。与荧光标记探针的结合试验表明，银杏酸直接结合E1并抑制E1-SUMO中间体的形成。这些研究不仅将为研究SUMO缀合在细胞多种信号通路中的作用提供有用工具，也为开发针对SUMO化异常相关疾病的药物奠定基础。