| Project/Area Number |
15K15581
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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 |
Urology
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2016-2017)
The University of Tokyo (2015) |
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Principal Investigator |
Takayama Ken-ichi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50508075)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | Prostate / p53 / Androgen / Nuclear export / G3BP2 / TRIM25 / USP10 / アンドロゲン受容体 / 前立腺癌 / ホルモン / 翻訳後修飾 / アンドロゲン / 転写制御 |
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| Outline of Final Research Achievements |
The androgen receptor (AR) has a central role in prostate cancer progression. Loss of the p53 tumor suppressor contributes to malignancy. We identified G3BP2 as a novel AR target involved in p53 signals by integrative sequence analysis. We then explored how G3BP2 modulates p53 activity and revealed that RanBP2, SUMO-E3 ligase, and TRIM25 are promising G3BP2-associating proteins in addition to known USP10. Mechanistically, translocation of p53 to cytoplasm was promoted by androgen-dependent sumoylation mediated by RanBP2. TRIM25 was indispensable for this complex formation and translocation of p53 to cytoplasm. Furthermore, G3BP2 expression is regulated at protein level through USP10-mediated inhibition of G3BP2 polyubiquitylation. Thus, G3BP2 has a repressive effect on p53 signaling through systematic interaction with RanBP2/TRIM25/USP10.
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