| Project/Area Number |
16K14724
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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 |
Cell biology
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| Research Institution | Gifu University (2017-2018)
Osaka University (2016) |
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Principal Investigator |
Kubori Tomoko 岐阜大学, 大学院医学系研究科, 准教授 (20397657)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ユビキチン / エフェクター / 脂質結合 / 液胞 / 病原細菌 / ゼノファジー |
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| Outline of Final Research Achievements |
Legionella is a Gram-negative bacterial pathogen that can deliver a large array of effector proteins into host eukaryotic cells to manipulate various cellular systems including the ubiquitin modification. Ubiquitin is known to conjugate exclusively with proteins. However, our analyses of ubiquitin accumulated on the bacterial vacuole raised the possibility of lipid-ubiquitin conjugation. By transfection of HeLa cells with latex beads, which mimics bacterial infection, we found that ubiquitin accumulated on the beads were subjected to modification. In order to examine the covalent binding of ubiquitin with lipid, we established the chemical synthesis of liposomes with combination of lipids. The result of in vitro analysis using Legionella effector proteins and the liposomes suggested that a bacterial ubiquitin ligase mediates the ubiquitin-lipid conjugation. Taken together, we raised the possibility of the non-canonical form of ubiquitin conjugation.
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| Academic Significance and Societal Importance of the Research Achievements |
ユビキチン修飾系は様々な局面で細胞内システムを文字どおり支配する重要な反応系である。従来、ユビキチン修飾の標的はタンパク質のみであると信じられてきた。一方、オートファジーに必須なユビキチン様タンパク質である LC3は脂質に結合することが広く知られている。我々は病原細菌を用いた感染実験を通じてユビキチンが脂質に共有結合する可能性を見出した。本研究課題ではリポソーム反応系などを用いてその可能性を確認するとともに、その活性を担う可能性を持つ新たな酵素を見出した。仮説の証明はユビキチン反応系の常識を塗り替える新たな概念の創出につながり、ユビキチンが介在する様々な疾患の予防や治療への基盤提供をもたらす。
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