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

    研究成果: Article

    50 引用 (Scopus)

    抄録

    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.

    元の言語English
    ページ(範囲)2635-2642
    ページ数8
    ジャーナルACS Chemical Biology
    8
    発行部数12
    DOI
    出版物ステータスPublished - 2013 12 20

    Fingerprint

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

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine

    これを引用

    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.

    :: ACS Chemical Biology, 巻 8, 番号 12, 20.12.2013, p. 2635-2642.

    研究成果: Article

    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, 巻. 8, 番号 12, pp. 2635-2642. https://doi.org/10.1021/cb400630z
    Hirohama M, Kumar A, Fukuda I, Matsuoka S, Igarashi Y, Saitoh H その他. Spectomycin B1 as a novel sumoylation inhibitor that directly binds to SUMO E2. ACS Chemical Biology. 2013 12 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. :: ACS Chemical Biology. 2013 ; 巻 8, 番号 12. pp. 2635-2642.
    @article{1fa135755b844799836a3923e15015fa,
    title = "Spectomycin B1 as a novel sumoylation inhibitor that directly binds to SUMO E2",
    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.",
    author = "Mikako Hirohama and Ashutosh Kumar and Isao Fukuda and Seiji Matsuoka and Yasuhiro Igarashi and Hisato Saitoh and Motoki Takagi and Kazuo Shin-Ya and Kaori Honda and Yasumitsu Kondoh and Tamio Saito and Youichi Nakao and Hiroyuki Osada and Zhang, {Kam Y J} and Minoru Yoshida and Akihiro Ito",
    year = "2013",
    month = "12",
    day = "20",
    doi = "10.1021/cb400630z",
    language = "English",
    volume = "8",
    pages = "2635--2642",
    journal = "ACS Chemical Biology",
    issn = "1554-8929",
    publisher = "American Chemical Society",
    number = "12",

    }

    TY - JOUR

    T1 - Spectomycin B1 as a novel sumoylation inhibitor that directly binds to SUMO E2

    AU - Hirohama, Mikako

    AU - Kumar, Ashutosh

    AU - Fukuda, Isao

    AU - Matsuoka, Seiji

    AU - Igarashi, Yasuhiro

    AU - Saitoh, Hisato

    AU - Takagi, Motoki

    AU - Shin-Ya, Kazuo

    AU - Honda, Kaori

    AU - Kondoh, Yasumitsu

    AU - Saito, Tamio

    AU - Nakao, Youichi

    AU - Osada, Hiroyuki

    AU - Zhang, Kam Y J

    AU - Yoshida, Minoru

    AU - Ito, Akihiro

    PY - 2013/12/20

    Y1 - 2013/12/20

    N2 - 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.

    AB - 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.

    UR - http://www.scopus.com/inward/record.url?scp=84890854989&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84890854989&partnerID=8YFLogxK

    U2 - 10.1021/cb400630z

    DO - 10.1021/cb400630z

    M3 - Article

    C2 - 24143955

    AN - SCOPUS:84890854989

    VL - 8

    SP - 2635

    EP - 2642

    JO - ACS Chemical Biology

    JF - ACS Chemical Biology

    SN - 1554-8929

    IS - 12

    ER -