Is ROS-sensing BAG-1/ATF4-system a regulatory system for ferroptosis?
Project/Area Number |
18K06630
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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Research Institution | Tohoku Medical and Pharmaceutical University |
Principal Investigator |
Kuge Shusuke 東北医科薬科大学, 薬学部, 教授 (50186376)
|
Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | BAG-1 / フェロトーシス / シスチントランスポーター / ヘムオキシゲナーゼ / がん細胞 / SLC7A11 / Ferroptosis / P53 / ROS感知 / xCT / eIF2α脱リン酸化 / eIF2αキナーゼ / リン酸化eIF2α脱リン酸化酵素 / ROS / ATF4 / eIF2alfa |
Outline of Final Research Achievements |
Ferroptosis is a novel regulatory cell death mediated by iron-dependent lipid peroxidation, and is attracting attention as cell death dependent on the cancer suppressor gene P53. So far, we have shown that BAG-1 senses intracellular ROS levels and induces transcription factor ATF4 synthesis and cystine transporter (xCT, SLC7A11) expression. Treatment with the xCT inhibitor Erastin to investigate non-xCT effects induced a marked increase in ROS levels and ferroptosis due to BAG-1 deficiency. BAG-1 has been shown to have the potential to negatively regulate ATF4 and HO-1 levels to suppress ferroptosis.
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Academic Significance and Societal Importance of the Research Achievements |
BAG-1はがん細胞に多く発現してその増殖や治療抵抗性に寄与することが示唆されているが、その分子機構は解明されていない。本研究は、細胞内酸化状態を感知してフェロトーシスを制御する分子機構を初めて示すと同時に、抗がん剤などによるフェロトーシスを介してがん細胞の増殖を抑制する過程でBAG-1が寄与する回避機構を解明するもので、がんの治療効率を上げる方法の開発につながる知見を与える。
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Report
(4 results)
Research Products
(25 results)