| Project/Area Number |
26293018
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SAEKI Yasushi 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副参事研究員 (80462779)
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| Research Collaborator |
YASUDA Sayaka 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 研究員 (80624353)
KAIHO Ai 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 研究補助員
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | プロテアソーム / ユビキチン / タンパク質分解 / リボソーム / タンパク質品質管理 / 細胞 / 生体分子 / 核内構造体 / ストレス応答 / 遺伝子 / 蛋白質 / 酵素 / プロテオーム / 転写 / クロマチン構造 |
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| Outline of Final Research Achievements |
The proteasome is the primary proteolytic machinery in cells and thus is a central regulator of the proteostasis network, but protein quality control (PQC) in the nucleus is largely unknown. Using EGFP knock-in cell lines of the proteasome subunit, we find that hyperosmotic stress induces rapid formation of nuclear foci of proteasomes within a few seconds. The foci are reversible structure that contains K48-linked ubiquitylated proteins, p97, and multiple proteasome-interacting proteins. The foci formation is dependent on ubiquitylation and their clearance requires active proteasomes, p97, and RAD23B, suggesting that this structure is a novel nuclear proteolytic center for adapting to nuclear stress. We identified ribosomal proteins as major ubiquitylated substrates that degraded in the foci, suggesting that the assembly process of the ribosome is vulnerable to hyperosmotic stress. Collectively, we identified the p97-RAD23B axis and the proteasome as a nuclear PQC pathway.
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