Identification of deubiquitinases, which regulate inflammatory and immune signaling pathways, and screening for their inhibitors
| Project/Area Number |
16K15210
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka City University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 酵素 / タンパク質 / 細胞・ 組織 / シグナル伝達 / 生体機能利用 / 免疫学 / バイオテクノロジー / 炎症 / 免疫 / ユビキチン / 酵素阻害剤 |
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| Outline of Final Research Achievements |
The deubiquitinating enzymes (DUBs) are proteases to antagonize ubiquitin modification system, and human genome encodes ~100 DUBs. In this study, we tried to identify DUBs, which regulate LUBAC- and linear ubiquitination-mediated NF-κB activation pathway. We found that HOIP is predominantly cleaved by caspase upon TNF-α-induced apoptosis. The N-terminal fragment of HOIP binds with DUBs, such as OTULIN and CYLD-SPATA2. In contrast, the C-terminal fragment of HOIP retains NF-κB activity, and linear ubiquitination of NEMO and FADD decreases upon apoptosis. These results indicate that caspase-mediated cleavage of HOIP divides critical functional regions of HOIP, and that this regulates linear (de)ubiquitination of substrates upon apoptosis.
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Report
(3 results)
Research Products
(29 results)
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[Journal Article] In-frame VIn-frame Val216-Ser217 deletion of KIT in mild piebaldism causes aberrant secretion and SCF response.2018
Author(s)
Hattori M, Ishikawa O, Oikawa D, Amano H, Yasuda M, Kaira K, Ishida-Yamamoto A, Nakano H, Sawamura D, Terawaki S, Wakamatsu K, Tokunaga F, Shimizu A
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Journal Title
J. Dermatol. Sci.
Volume: -
Related Report
Peer Reviewed
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[Journal Article] Mechanistic insight into the repigmentation of piebaldism: functional characterization of a mutant KIT in melanocyte regeneration.2018
Author(s)
Hattori M, Oikawa D, Amano H, Yasuda M, Kaira K, Ishida-Yamamoto A, Nakano H, Sawamura D, Terawaki S, Wakamatsu K, Tokunaga F, Ishikawa O, Shimizu A.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] HTLV-1 Tax induces formation of the active macromolecular IKK complex by generating Lys63- and Met1-linked hybrid polyubiquitin chains.2017
Author(s)
Shibata Y, Tokunaga F, Goto E, Komatsu G, Gohda J, Saeki Y, Tanaka K, Takahashi H, Sawasaki T, Inoue S, Oshiumi H, Seya T, Nakano H, Tanaka Y, Iwai K, and Inoue J.
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Journal Title
PLoS Pathog.
Volume: 13
Issue: 12
Pages: e1006162-e1006162
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Reduced SHARPIN and LUBAC formation may contribute to CCl4- or acetaminophen-induced liver cirrhosis in mice.2017
Author(s)
Yamamotoya T, Nakatsu Y, Matsunaga Y, Fukushima T, Yamazaki H, Kaneko S, Fujishiro M, Kikuchi T, Kushiyama A, Tokunaga F, Asano T, and Sakoda H.
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Journal Title
Int. J. Mol. Sci.
Volume: 18
Issue: 2
Pages: 326-326
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Linear ubiquitination is involved in the pathogenesis of optineurin-associated amyotrophic lateral sclerosis.2016
Author(s)
Nakazawa S, Oikawa D, Ishii R, Ayaki T, Takahashi H, Takeda H, Ishitani R, Kamei K, Takeyoshi I, Kawakami H, Iwai K, Hatada I, Sawasaki T, Ito H, Nureki O, and Tokunaga F.
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Journal Title
Nat. Commun.
Volume: 7
Issue: 1
Pages: 12547-12547
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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