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

被引：323

作者：

Fukuda, Isao ^{[1
,2
]}

Ito, Akihiro ^{[1
,3
,4
]}

Hirai, Go ^{[3
,5
]}

Nishimura, Shinichi ^{[1
]}

Kawasaki, Hisashi ^{[6
]}

Saitoh, Hisato ^{[7
]}

Kimura, Ken-ichi ^{[8
]}

Sodeoka, Mikiko ^{[3
,5
]}

Yoshida, Minoru ^{[1
,2
,3
,4
]}

机构：

[1] RIKEN, Adv Sci Inst, Chem Genet Lab, Wako, Saitama 3510198, Japan

[2] Saitama Univ, Grad Sch Sci & Engn, Saitama 3388570, Japan

[3] RIKEN, Adv Sci Inst, Chem Genom Res Grp, Wako, Saitama 3510198, Japan

[4] CREST Res Project, Japan Sci & Technol Corp, Kawaguchi, Saitama 3320012, Japan

[5] RIKEN, Adv Sci Inst, Synthet Organ Chem Lab, Wako, Saitama 3510198, Japan

[6] Tokyo Denki Univ, Dept Green & Sustainable Chem, Chiyoda Ku, Tokyo 1018457, Japan

[7] Kumamoto Univ, Inst Mol Embryol Genet, Dept Regulat Med, Kumamoto 8600811, Japan

[8] Iwate Univ, Fac Agr, Dept Agrobiosci, Biol Chem Lab, Morioka, Iwate 0208550, Japan

来源：

CHEMISTRY & BIOLOGY | 2009年 / 16卷 / 02期

关键词：

UBIQUITIN-ACTIVATING ENZYME; HISTONE ACETYLTRANSFERASE; SUMO; KINASE; CANCER; P53;

D O I：

10.1016/j.chembiol.2009.01.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：133 / 140

页数：8

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