Elucidation of novel molecular mechanisms in the regulation of stress-responsive signaling by cross talk of various post-translational modifications
| Project/Area Number |
18H02567
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Tohoku University |
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 翻訳後修飾 / シグナル伝達 / ストレス応答 / リン酸化 / ユビキチン化 |
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| Outline of Final Research Achievements |
The strict regulation of duration and intensity of activation of the stress response signaling is required for the induction of appropriate responses to various types of internal and external stress, and its failure causes cellular dysfunction and various diseases. However, the molecular mechanisms of the regulation are not well understood. In this study, we found that the balance of the stress response signaling is actually regulated and fine-tuned through the crosstalk (cooperative and reciprocal interaction) between various post-translational modifications, such as ubiquitination, for kinases as signaling molecules essential for the induction of stress responses, including cell death and inflammation, and that the disorder of the balance could lead to the onset of cancer and autoimmune diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
様々な内外環境ストレスに適応し、細胞死や炎症などの適切なストレス応答を誘導することで、生体や細胞はその恒常性を維持しているため、ストレス応答シグナルのバランスが破綻すると多様な疾患に陥る。本研究において、ストレス応答シグナルのバランス制御が、キナーゼのようなストレス応答シグナル分子に対する、ユビキチン化等の多彩な翻訳後修飾のクロストークで実際に制御・微調整されることを見出し、そのユビキチン化酵素やキナーゼ分子の異常が癌・自己免疫疾患等の発症に結び付く可能性を示せた点は、それらの疾患の原因解明と具体的な新規創薬標的分子の特定に繋がり、新規疾患治療戦略の提言を可能とする重要な研究成果である。
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Report
(4 results)
Research Products
(122 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] Redox cycling of 9,10-phenanthrenequinone activates epidermal growth factor receptor signaling through <i>S</i>-oxidation of protein tyrosine phosphatase 1B2020
Author(s)
Luong, N. C., Abiko, Y., Shibata, T., Uchida, K., Warabi, E., Suzuki, M., Noguchi, T., Matsuzawa, A., Kumagai, Y.
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Journal Title
The Journal of Toxicological Sciences
Volume: 45
Issue: 12
Pages: 807-807
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Characterization of PC12 cell subclones with different sensitivities to programmed thermal stimulation.2020
Author(s)
Kudo, T., Tominami, K., Izumi, S., Hayashi, Y., Noguchi, T., Matsuzawa, A., Hong, G., Nakai, J.
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Journal Title
Int. J. Mol. Sci.
Volume: 21
Issue: 21
Pages: 8356-8356
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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[Journal Article] The antibiotic cefotaxime works as both an activator of Nrf2 and an inducer of HSP70 in mammalian cells.2020
Author(s)
Yamada, M., Suzuki, M., Noguchi, T., Yokozawa, T., Sekiguchi, Y., Mutoh, N., Toyama, T., Hirata, Y., Hwang, G. W., Matsuzawa, A.
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Journal Title
BPB Rep.
Volume: 3
Pages: 16-21
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Functional interaction between PXR and YAP in xenobiotic-dependent liver hypertrophy and drug metabolism.2019
Author(s)
Abe, T., Shizu, R., Sasaki, T., Shimizu, Y., Hosaka, T., Kodama, S., Matsuzawa, A., Yoshinari, K.
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Journal Title
J. Pharmacol. Exp. Ther.
Volume: 371
Issue: 3
Pages: 590-601
DOI
Related Report
Peer Reviewed
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[Journal Article] Antibiotic vancomycin promotes the gene expression of NOD-Like receptor families in macrophages.2018
Author(s)
Kudo, Y., Noguchi, T., Ishii, C., Maeda, K., Nishidate, A., Hirata, Y., Matsuzawa, A.
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Journal Title
BPB Rep.
Volume: 1
Pages: 6-10
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Role of YAP Activation in Nuclear Receptor CAR-Mediated Proliferation of Mouse Hepatocytes.2018
Author(s)
Abe, T., Amaike, Y., Shizu, R., Takahashi, M., Kano, M., Hosaka, T., Sasaki, T., Kodama, S., Matsuzawa, A., Yoshinari, K.
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Journal Title
Toxicol Sci.
Volume: 165
Issue: 2
Pages: 408-419
DOI
Related Report
Peer Reviewed
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