2. Academic Validation
  3. Spectomycin B1 as a novel SUMOylation inhibitor that directly binds to SUMO E2

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

  • ACS Chem Biol. 2013 Dec 20;8(12):2635-42. doi: 10.1021/cb400630z.
Mikako Hirohama 1,  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
Affiliations

Affiliation

  • 1 Chemical Genetics Laboratory, ‡Zhang Initiative Research Unit, §Antibiotics Laboratory, RIKEN, ∥Drug Discovery Platforms Cooperation Division, ⊥Chemical Biology Research Group, #Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
PMID: 24143955 DOI: 10.1021/cb400630z
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.

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