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, Youichi Nakao, Hiroyuki Osada, Kam Y J Zhang, Minoru Yoshida, Akihiro Ito

    Research output: Contribution to journalArticle

    49 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

    Fingerprint

    Sumoylation
    Ubiquitin
    Biological systems
    Breast Neoplasms
    Biological Products
    Screening
    Estrogens
    Proteins
    Cells
    Hormones
    ginkgolic acid

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine

    Cite this

    Hirohama, M., Kumar, A., Fukuda, I., Matsuoka, S., Igarashi, Y., Saitoh, H., ... 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

    Spectomycin B1 as a novel sumoylation inhibitor that directly binds to SUMO E2. / Hirohama, Mikako; Kumar, Ashutosh; Fukuda, Isao; Matsuoka, Seiji; Igarashi, Yasuhiro; Saitoh, Hisato; Takagi, Motoki; Shin-Ya, Kazuo; Honda, Kaori; Kondoh, Yasumitsu; Saito, Tamio; Nakao, Youichi; Osada, Hiroyuki; Zhang, Kam Y J; Yoshida, Minoru; Ito, Akihiro.

    In: ACS Chemical Biology, Vol. 8, No. 12, 20.12.2013, p. 2635-2642.

    Research output: Contribution to journalArticle

    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, KYJ, Yoshida, M & Ito, A 2013, 'Spectomycin B1 as a novel sumoylation inhibitor that directly binds to SUMO E2', ACS Chemical Biology, vol. 8, no. 12, pp. 2635-2642. https://doi.org/10.1021/cb400630z
    Hirohama M, Kumar A, Fukuda I, Matsuoka S, Igarashi Y, Saitoh H et al. Spectomycin B1 as a novel sumoylation inhibitor that directly binds to SUMO E2. ACS Chemical Biology. 2013 Dec 20;8(12):2635-2642. https://doi.org/10.1021/cb400630z
    Hirohama, Mikako ; Kumar, Ashutosh ; Fukuda, Isao ; Matsuoka, Seiji ; Igarashi, Yasuhiro ; Saitoh, Hisato ; Takagi, Motoki ; Shin-Ya, Kazuo ; Honda, Kaori ; Kondoh, Yasumitsu ; Saito, Tamio ; Nakao, Youichi ; Osada, Hiroyuki ; Zhang, Kam Y J ; Yoshida, Minoru ; Ito, Akihiro. / Spectomycin B1 as a novel sumoylation inhibitor that directly binds to SUMO E2. In: ACS Chemical Biology. 2013 ; Vol. 8, No. 12. pp. 2635-2642.
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