Гинколовата киселина е токсичен агент, който инхибира СУМОилирането на протеините (small ubiquitin-related modifier proteins -SUMO)
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Гинколовата киселина е токсичен агент, който инхибира СУМОилирането на протеините (small ubiquitin-related modifier proteins -SUMO)

Гинколовата киселина е токсичен агент, който инхибира СУМОилирането на протеините (small ubiquitin-related modifier proteins -SUMO)

Isao Fukuda,1,2 Akihiro Ito,1,3,4,* Go Hirai,3,5 Shinichi Nishimura,1 Hisashi Kawasaki,6 Hisato Saitoh,7 Ken-ichi Kimura,8 Mikiko Sodeoka,3,5 and Minoru Yoshida1,2,3,4

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.

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Ginkgolic Acid Inhibits Protein SUMOylation by Blocking Formation of the E1-SUMO Intermediate
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