| 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
|
| Project Status |
Completed (Fiscal Year 2017)
|
| 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 |
|---|
| 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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