| Project/Area Number |
26860188
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
Nakagawa Tomoko 京都大学, 医学(系)研究科(研究院), 研究員 (90623976)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | シグナル伝達 / NF-kappaB / ユビキチン |
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| Outline of Final Research Achievements |
I have shown that OTULIN and CYLD, which are deubiquitinating enzymes (DUBs) cleaving linear ubiquitin chains specifically, down-regulate NF-κB activation by binding to HOIP, a subunit of LUBAC. Based on my original findings, I dissected the physiological roles of coordinated synthesis and cleavage of linear ubiquitination by co-existing its ligase and DUBs in this research proposal. Using OTULIN conditional knockout mice, I have dissected the roles of coordinated synthesis and cleavage of linear ubiquitination in B and T lymphocytes. To my disappointment, I could not found any abnormality in OTULIN null T or B cells. However, in collaboration with the research group in Hokkaido University, I start dissecting the molecular mechanisms underlying hyper-inflammatory symptoms found in a patient having mutations in OTULIN genes and found that inflammation provoked by pathogens could not be terminated because of the attenuated DUB activity of OTULIN.
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