TY - JOUR
T1 - Ginkgolic Acid Inhibits Protein SUMOylation by Blocking Formation of the E1-SUMO Intermediate
AU - Fukuda, Isao
AU - Ito, Akihiro
AU - Hirai, Go
AU - Nishimura, Shinichi
AU - Kawasaki, Hisashi
AU - Saitoh, Hisato
AU - Kimura, Ken ichi
AU - Sodeoka, Mikiko
AU - Yoshida, Minoru
N1 - Funding Information:
We thank Y. Uchimura (Kumamoto University) for a technical suggestion. This work was supported in part by the Chemical Genomics Research Group Project, RIKEN Advanced Science Institute, the CREST Research Project, the Japan Science and Technology Corporation, and a Grant-in-Aid for Scientific Research on Priority Area “Cancer” from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2009/2/27
Y1 - 2009/2/27
N2 - 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.
AB - 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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U2 - 10.1016/j.chembiol.2009.01.009
DO - 10.1016/j.chembiol.2009.01.009
M3 - Article
C2 - 19246003
AN - SCOPUS:60649088334
SN - 2451-9448
VL - 16
SP - 133
EP - 140
JO - Cell Chemical Biology
JF - Cell Chemical Biology
IS - 2
ER -
