Ginkgolic acid inhibits protein SUMOylation by blocking formation of the E1-SUMO intermediate.
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.
Fukuda
Isao
I
Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.
Ito
Akihiro
A
Hirai
Go
G
Nishimura
Shinichi
S
Kawasaki
Hisashi
H
Saitoh
Hisato
H
Kimura
Ken-Ichi
K
Sodeoka
Mikiko
M
Yoshida
Minoru
M
D048729:Anacardic Acids / Q000737:chemistry / Q000378:metabolism*; D020441:Ginkgo biloba / Q000737:chemistry / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012459:Salicylates / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries; D025841:Small Ubiquitin-Related Modifier Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D054875:Ubiquitination
D048729:Anacardic Acids; D010936:Plant Extracts; D012459:Salicylates; D054852:Small Molecule Libraries; D025841:Small Ubiquitin-Related Modifier Proteins; C088115:anacardic acid; C112485:ginkgolic acid