| Project/Area Number |
16K18442
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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 |
Tumor diagnostics
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Shimomura Masanori 京都府立医科大学, 医学(系)研究科(研究院), 助教 (90433268)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | パクリタキセル / FIGNL1 / 抗がん剤耐性機序 / パクリタキセル耐性機序 / FGNL1 / パクリタキセル関連タンパク質 / 薬効評価と予測 / パクリタキセル耐性関連タンパク |
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| Outline of Final Research Achievements |
We have identified human FIGNL1 as a candidate of paclitaxel binding protein with an affinity pull-down method followed by LC-MS/MS. Higher expression of FIGNL1 protein was detected in the drug-resistant lung cancer cell line than in the sensitive ones. We observed that cytoplasmic FIGNL1 is frequently attached to acetylated tubulin in microtubules with super-resolution fluorescent microscopy, and that FIGNL1 knock-downed cell had a tendency of increase in both polymerization and acetylation of tubulins and decrease in paclitaxel resistance. Stabilization of tubulins by paclitaxel may be antagonized by the severing activity of FIGNL1. Now, in silico protein-ligand docking analysis did not predict the binding of the drug to the catalytic domain but to the surface pocket newly formed in a FIGNL1 dimer. Because the octamer of Fidgetin is known to be its active form, we speculate that the drug contributes to the binding to the active form, enhancing the above antagonistic action.
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| Academic Significance and Societal Importance of the Research Achievements |
パクリタキセルはチュブリンに結合して微小管の重合化及び安定化を促進することで抗腫瘍効果をきたすとされている．パクリタキセルの感受性を規定する因子は未だ十分に解明されていない
われわれはプロテオーム解析を経て得られたパクリタキセル結合タンパク質の同定を行った．そのひとつとしてFIGNL1タンパクが同定され，安定化したアセチル化チュブリンに結合しそれらを切断することで微小管の不安定化をきたし薬剤耐性が生じている可能性が考えられた．新たな耐性機構の解明につながる成果であり，薬剤耐性克服の一助になる可能性を考えている．
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