Development of regulators of the LUBAC ubiquitin ligase that modulate NF-kappaB activation
Project/Area Number |
24659136
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Single-year Grants |
Research Field |
General medical chemistry
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Research Institution | Kyoto University |
Principal Investigator |
IWAI Kazuhiro 京都大学, 医学(系)研究科(研究院), 教授 (60252459)
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Project Period (FY) |
2012-04-01 – 2014-03-31
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | 細胞内シグナル伝達 / シグナル伝達 / 直鎖状ポリユビキチン鎖 / 慢性皮膚炎 / NF-kappaB / 直鎖状ポリユビキチン鎖生成阻害剤 |
Research Abstract |
NF-kappaB is a family of a transcription factor that involves in various biologcal phenomena including inflammation, immune responses, and cell survival. Abnormal activation NF-kappaB is also known to be related to the pathogenesis of various diseases. Thus, regulation of NF-kappaB is a suitable target of drugs for those diseases. Since we have identified LUBAC-mediated linear polyubiquitination is involved in NF-kappaB activation, we tried to develop the agents that up-regulate or inhibit LUBAC's ligase activity. We then identified a small chemical that inhibits LUBAC-mediated linear polyubiquitination and NF-kappaB actvation. Also, we found that interferon-gamma increases the amount of LUBAC and enhances NF-kappaB actvation.
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] Suppression of LUBAC-mediated linear ubiquitination by a specific interaction between LUBAC and the deubiquitinases CYLD and OTULIN.2014
Author(s)
Takiuchi, T., Nakagawa, T., Tamiya, H., Fujita, H., Sasaki, Y., Saeki, Y., Takeda, H., Sawasaki, T., Buchberger, A., Kimura, T., and Iwai. K.
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Journal Title
Genes Cells.
Volume: 19
Issue: 3
Pages: 254-272
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Mechanism underlying IKK activation mediated by the linear ubiquitin chain assembly complex (LUBAC).2014
Author(s)
Fujita, H., Rahighi, S., Akita, M., Kato, R., Sasaki, Y., Wakatsuki, S., and Iwai, K.
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Journal Title
Mol. Cell. Biol.
Volume: 34
Issue: 7
Pages: 1322-1335
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells2013
Author(s)
Sasaki, Y., Sano, S., Nakahara, M., Murata, S., Kometani, K., Aiba, Y., Sakamoto, S., Watanabe, Y., Tanaka, K., Kurosaki, T., and lwai, K.
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Journal Title
EMBO J.
Volume: 32
Issue: 18
Pages: 2463-2476
DOI
Related Report
Peer Reviewed
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