2013 Fiscal Year Final Research Report
Study on chemical biology for protein SUMOylation
| Project/Area Number |
23510288
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
ITO Akihiro 独立行政法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (40391859)
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| Co-Investigator(Renkei-kenkyūsha) |
HIRAI Go 独立行政法人理化学研究所, 袖岡有機合成化学研究室, 専任研究員 (50359551)
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| Project Period (FY) |
2011 – 2013
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| Keywords | SUMO / 阻害剤 / 抗がん剤 / 脱SUMO化酵素 |
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| Research Abstract |
The aim of this study is to elucidate roles of protein SUMOylation in carcinogenesis using a chemical biology approach. Using an in situ cell-based SUMOylation assay system, we identified several small molecule inhibitors of SUMOylation including spectomycin B1 as SUMO E2 (Ubc9) inhibitor. Our findings suggested that Ubc9 inhibitors such as spectomycin B1 have a potential as a therapeutic agent against ERalpha-dependent breast cancers. Furthermore, we identified a novel deSUMOylatuon enzyme, SENP1, inhibitor by an in situ deSUMOylation assay. We found that SENP1 inhibitor reduced the activity of HIF-1alpha,an important transcriptional factor for cancer survival under hypoxia microenvironment. In addition, we succeeded in developing novel assay systems for detecting non-covalent interactions between SUMO and SIM using a split-luciferase complementation and identified first small molecules that inhibit SUMO-dependent protein-protein interactions.
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Research Products
(20 results)
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[Journal Article] Inhibition of protein SUMOylation by davidiin, an ellagitannin from Davidia involucrate2013
Author(s)
Takemoto M, Kawamura Y, Hirohama M, Yamaguchi Y, Handa H, Saitoh H, Nakao Y, Kawada M, Khalid K, Koshino H, Kimura K, Ito A, Minoru Yoshida M.
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Journal Title
J. Antibiot.
Volume: 67
Pages: 335-8
DOI
Peer Reviewed
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[Journal Article] Spectomycin B1 as a Novel SUMOylation Inhibitor That Directly Binds to SUMO E22013
Author(s)
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 KY, Yoshida M, Ito A.
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Journal Title
ACS Chem, Biol.
Volume: 8
Pages: 2635-42
DOI
Peer Reviewed
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