Study on two ubiquitin ligases involved in inflammation and immune signal regulation
| Project/Area Number |
18H02619
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Osaka City University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | タンパク質 / 酵素 / 細胞 / 炎症 / ユビキチン |
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| Outline of Final Research Achievements |
In this study, we identified two novel RING-type ubiquitin ligases (E3s), which bind and modulate LUBAC, a sole E3 to generate Met1-linked linear ubiquitin chain and activate NF-κB signaling. Among them, LUBAC-associated protein 1 (LAP1) suppressed LUBAC function and affected the cell death response, whereas LAP2 was found to further enhance NF-κB signal via K63 ubiquitination activity.
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| Academic Significance and Societal Importance of the Research Achievements |
最近、ユビキチン鎖は均一の連結鎖で構成されるのではなく、分岐鎖や混合鎖など複数の連結鎖からなる複雑な形態を呈することで、多彩な細胞機能を微調節することが明らかになってきた。本研究で我々は、直鎖状ユビキチン鎖生成を介して炎症や免疫制御に重要なNF-κBシグナル経路を活性化するLUBACユビキチンリガーゼ(E3)と共役する2種の新規E3(LAP1とLAP2)を見出し、炎症・細胞死への影響を解明した。LUBACとLAP1、LAP2との相互作用は、炎症や細胞死を制御しており、神経変性疾患におけるユビキチン陽性封入体の経時的な凝集、タンパク質分解に対す抵抗性、炎症の遷延、細胞死に関わる可能性がある。
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Report
(4 results)
Research Products
(65 results)
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[Journal Article] Capacity of extracellular globins to reduce liver fibrosis via scavenging reactive oxygen species and promoting MMP-1 secretion.2022
Author(s)
Hieu VN, Thuy LTT, Hai H, Dat NQ, Hoang DV, Hanh NV, Phuong DM, Hoang TH, Sawai H, Shiro Y, Sato-Matsubara M, Oikawa D, Tokunaga F, Yoshizato K, Kawada N.
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Journal Title
Redox Biol.
Volume: 52
Pages: 102286-102286
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Molecular bases for HOIPINs-mediated inhibition of LUBAC and innate immune responses.2020
Author(s)
Oikawa D, Sato Y, Ohtake F, Komakura K, Hanada K, Sugawara K, Terawaki S, Mizukami Y, Phuong HT, Iio K, Obika S, Fukushi M, Irie T, Tsuruta D, Sakamoto S, Tanaka K, Saeki Y, Fukai S, Tokunaga F.
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Journal Title
Commun. Biol.
Volume: 3
Issue: 1
Pages: 163-163
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Screening and characterization of novel LUBAC inhibitors, HOIPINs2019
Author(s)
Oikawa, D., Katsuya, K., Hanada, K., Sugawara, K., Tsuruta, D., Sakamoto, S., Tokunaga, F.
Organizer
Cold Spring Harbor Laboratory Meeting on Ubiquitin, Autophagy & Disease
Related Report
Int'l Joint Research
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