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

Full 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.

Author information

Author/s: Fukuda, Isao (I); 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);

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

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Chemistry & biology (Chem Biol), published in United States. (Language: eng)

Reference: 2009-Feb; vol 16 (issue 2) : pp 133-40

Dates: Created 2009/02/27; Completed 2009/06/09;

PMID: 19246003, status: MEDLINE (last retrieval date: 6/9/2009, IMS Date: 09 Jun 2009 00:00:00)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Anacardic Acids - chemistry; metabolism
Ginkgo biloba - chemistry; metabolism
Plant Extracts - chemistry; metabolism
Plant Leaves - chemistry; metabolism
Protein Binding

Associated Chemicals: Anacardic Acids (0) ; Plant Extracts (0) ; Salicylic Acids (0) ; Small Molecule Libraries (0) ; Small Ubiquitin-Related Modifier Proteins (0) ; anacardic acid (18654-18-7) ; ginkgolic acid (22910-60-7)

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