| Project/Area Number |
25440097
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Cell biology
|
|---|
| Research Institution | Institute of Physical and Chemical Research |
|---|
Principal Investigator |
Mizuno Takeshi 国立研究開発法人理化学研究所, 今本細胞核機能研究室, 専任研究員 (30281629)
|
|---|
| Project Period (FY) |
2013-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | タンパク質品質管理 / 哺乳類細胞品質管理 / DNAポリメラーゼα / 温度感受性変異体細胞 / Novobiocin / HSP90 / タンパク質分解 / 哺乳類細胞核 / 細胞核 / テロメア / pot1 / シェルタリン / ラギング鎖合成 / 核内タンパク質品質管理 / 核内タンパク質分解 / 温度感受性変異体 / ノボビオシン / tsFT20 / 核内変性タンパク質分解 / CHIP / 品質管理 / 塩化コバルト / NIH3t3細胞 / 核内品質管理 / HSP９０ / novobiocin / プロテアソーム |
|---|
| Outline of Final Research Achievements |
Due to a single point mutation in the DNA Polymerase alpha subunit p180, the temperature-sensitive cell cycle mouse cell line tsFT20 reveals a rapid de novo synthesis of p180tsFT20 in the cytoplasm and a proteasome-dependent degradation of nuclear localized protein. To further analyze the mechanism of nuclear degradation of aberrant Pol-alpha, we have searched chemicals those inhibit degradation of nuclear aberrant p180. We found that novobiocin, an HSP90 inhibitor, inhibits degradation of p180tsFT20 at non-permissive temperature in nucleus. To identify molecule participate in nuclear protein quality control, we carried out co-immunoprecitation analysis, and found that Chip (C terminus of Hsc-70 interacting protein) associated with HSP90 and colocalized in the nucleolus in the presence of novobiocin. Taken together, we have a working hypothesis that nuclear protein quality control mechanism involves nuclear HSP90.
|
