Elucidation of the regulatory mechanisms of ASK1 ubiquitination for developing a new treatment strategy for ASK1-related diseases
| Project/Area Number |
15K18856
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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 |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
Hirata Yusuke 東北大学, 薬学研究科, 助教 (10748221)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ASK1 / Roquin-2 / TRIM48 / ユビキチン化 / TLR4 / 免疫応答 |
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| Outline of Final Research Achievements |
Roquin-2 is a ubiquitin ligase that ubiquitinates a stress-responsive kinase ASK1. In this study, we identified another ubiquitination target of Roquin-2 that functions in TLR4 (the receptor for a bacterial component, LPS) signaling pathway. We found that Roquin-2 promotes ubiquitin-dependent degradation of ASK1 and the newly found target molecule, and thereby negatively regulates innate immune responses. Meanwhile, we also identified another ubiquitin ligase TRIM48 as a positive regulator of ASK1 activation. TRIM48 promotes ASK1 activation, and thus facilitates ASK1 ubiquitination mediated by Roquin-2. These findings provide comprehensive understanding of the regulatory mechanisms for ASK1 ubiqutination, which will lead to the development of novel therapeutic strategies for ASK1-related diseases.
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Trans-fatty acids promote proinflammatory signaling and cell death by stimulating the apoptosis signal-regulating kinase 1 (ASK1)-p38 pathway.2017
Author(s)
Hirata, Y., Takahashi, M., Kudoh, Y., Kano, K., Kawana, H., Makide, K., Shinoda, Y., Yabuki, Y., Fukunaga, K., Aoki, J., Noguchi, T., Matsuzawa, A.
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Journal Title
J. Biol. Chem.
Volume: 印刷中
Issue: 20
Pages: 8174-8185
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Brefeldin A-inhibited guanine nucleotide-exchange factor 1 (BIG1) governs the recruitment of tumor necrosis factor receptor-associated factor 2 (TRAF2) to tumor necrosis factor receptor 1 (TNFR1) signaling complexes.2016
Author(s)
Noguchi, T., Tsuchida, M., Kogue, Y., Spadini, C., Hirata, Y., Matsuzawa, A.
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Journal Title
Int. J. Mol. Sci.
Volume: 17
Issue: 11
Pages: 1869-1869
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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