Elucidation of balancing mechanisms of death receptor signaling mediated by STK11
Project/Area Number |
18K06622
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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 University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | アポトーシス / STK11 / キナーゼ / Fas / シグナル伝達 / Fasリガンド / カスパーゼ / RNAiスクリーニング / プロテインキナーゼ / TNF受容体 / FAS |
Outline of Final Research Achievements |
Fas-induced apoptosis is mediated by tow pathways, "internal pathway" and "external pathway", depending on whether or not mitochondrial outer membrane permeation is required. This study revealed that STK11 activates the external pathway by promoting the degradation of the anti-apoptotic factor XIAP. In addition, under the condition that the signal of the internal pathway is sufficiently transmitted, STK11 promotes PARP-dependent nuclear translocation of AIF and induces programmed cell death called parthanatos to enhance the activation of the internal pathway.
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Academic Significance and Societal Importance of the Research Achievements |
本研究の結果明、細胞死促進因子として我々が独自に同定したSTK11が、状況依存的に別々の機構を活性化することでFas誘導性アポトーシスの感受性を亢進させていることが明らかとなった。癌抑制遺伝子としてのSTK11の新たな腫瘍抑制機構 の発見は、癌研究領域での学術的意義が高い。また、STK11を介したアポトーシスシグナルSTK11によるFasシグナル制御機構を明らかにすることは、癌抑制遺伝子として注目されているSTK11を標的とした治療薬の有効性を担保する強力な科学的裏付けとなり、その治療薬開発に具体性と確実性をもたらす。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Gefitinib initiates sterile inflammation by pomoting IL-1β and HMGB1 release via two distinct mechanisms2021
Author(s)
Takuya Noguchi, Yuto Sekiguchi, Yuki Kudoh, Rio Naganuma, Tomohiro Kagi, Akiko Nishidate, Kazuhiro Maeda, Chizuru Ishii, Takashi Toyama, Yusuke Hirata, Gi-Wook Hwang, Atsushi Matsuzawa
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Journal Title
Cell Death. Dis.
Volume: 12
Issue: 1
Pages: 49-49
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pro-apoptotic functions of TRAF2 in p53-mediated apoptosis induced by cisplatin2020
Author(s)
Tsuchida, M., Yokozawa, T., Noguchi, T., Shimada, T., Yamada, M., Sekiguchi, Y., Hirata, Y., Matsuzawa, A.
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Journal Title
The Journal of Toxicological Sciences
Volume: 45
Issue: 4
Pages: 219-226
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Open Access
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