Spectomycin B1 as a novel sumoylation inhibitor that directly binds to SUMO E2

Mikako Hirohama, Ashutosh Kumar, Isao Fukuda, Seiji Matsuoka, Yasuhiro Igarashi, Hisato Saitoh, Motoki Takagi, Kazuo Shin-Ya, Kaori Honda, Yasumitsu Kondoh, Tamio Saito, Yoichi Nakao, Hiroyuki Osada, Kam Y.J. Zhang, Minoru Yoshida, Akihiro Ito

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Conjugation of small ubiquitin-like modifier (SUMO) to protein (SUMOylation) regulates multiple biological systems by changing the functions and fates of a large number of proteins. Consequently, abnormalities in SUMOylation have been linked to multiple diseases, including breast cancer. Using an in situ cell-based screening system, we have identified spectomycin B1 and related natural products as novel SUMOylation inhibitors. Unlike known SUMOylation inhibitors such as ginkgolic acid, spectomycin B1 directly binds to E2 (Ubc9) and selectively blocks the formation of the E2-SUMO intermediate; that is, Ubc9 is the direct target of spectomycin B1. Importantly, either spectomycin B1 treatment or Ubc9 knockdown inhibited estrogen-dependent proliferation of MCF7 human breast-cancer cells. Our findings suggest that Ubc9 inhibitors such as spectomycin B1 have potential as therapeutic agents against hormone-dependent breast cancers.

Original languageEnglish
Pages (from-to)2635-2642
Number of pages8
JournalACS Chemical Biology
Volume8
Issue number12
DOIs
Publication statusPublished - 2013 Dec 20

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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    Hirohama, M., Kumar, A., Fukuda, I., Matsuoka, S., Igarashi, Y., Saitoh, H., Takagi, M., Shin-Ya, K., Honda, K., Kondoh, Y., Saito, T., Nakao, Y., Osada, H., Zhang, K. Y. J., Yoshida, M., & Ito, A. (2013). Spectomycin B1 as a novel sumoylation inhibitor that directly binds to SUMO E2. ACS Chemical Biology, 8(12), 2635-2642. https://doi.org/10.1021/cb400630z