Molecular basis of physiological and pathological regulation by endoplasmic reticulum stress response
Project/Area Number |
17H01424
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Functional biochemistry
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Research Institution | Hiroshima University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥42,900,000 (Direct Cost: ¥33,000,000、Indirect Cost: ¥9,900,000)
Fiscal Year 2019: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2018: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2017: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
|
Keywords | 細胞・組織 / シグナル伝達 / 細胞生物学 / 小胞体ストレス / ストレスセンサー |
Outline of Final Research Achievements |
We focused on the metabolism, activation, and intracellular function of BBF2H7 and OASIS, that are endoplasmic reticulum stress sensors, and analyzed the details of the physiological roles they have. 1) We found that small peptide derived from BBF2H7 is produced in response to ER stress, and the peptide is easy to aggregate, suggesting that the proteolysis of BBF2H7 dependent on ER stress may be involved in the pathogenesis of neurodegenerative diseases. 2) p21 was identified as a transcription target of OASIS, which was proven to be a cellular senescence-promoting factor. We succeeded in developing a new cancer treatment strategy to stop the cell growth of cancer cells by epigenome editing of oasis gene that was methylated at its promoter region. 3) The mucopolysaccharide-causing molecule IDS is degraded by ERAD pathway. Folding of mutant IDS was promoted through activation of calnexin cycle by blocking the ERAD pathway and the activities of mutant IDS was found to be recovered.
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Academic Significance and Societal Importance of the Research Achievements |
小胞体ストレス応答機構が小胞体以外のオルガネラ機能に大きな影響を与えていることを分子実体として証明した学術的意義は大きい。また、それらの機能制御が神経変性疾患、癌、希少難病の治療につながる可能性を見出したことは社会的にも意義深い。
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Report
(4 results)
Research Products
(62 results)
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[Journal Article] NFAT5 up-regulates expression of the kidney-specific ubiquitin ligase gene Rnf183 under hypertonic conditions in inner-medullary collecting duct cells.2019
Author(s)
Maeoka Y, Wu Y, Okamoto T, Kanemoto S, Guo XP, Saito A, Asada R, Matsuhisa K, Masaki T, Imaizumi K, Kaneko M.
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Journal Title
J Biol Chem.
Volume: 294
Issue: 1
Pages: 101-115
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Shutdown of ER-associated degradation pathway rescues functions of mutant iduronate 2-sulfatase linked to mucopolysaccharidosis type II.2018
Author(s)
Osaki Y, Saito A, Kanemoto S, Kaneko M, Matsuhisa K, Asada R, Masaki T, Orii K, Fukao T, Tomatsu S, Imaizumi K
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Journal Title
Cell Death Dis.
Volume: 9
Issue: 8
Pages: 808-808
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sec16A, a key protein in COPII vesicle formation, regulates the stability and localization of the novel ubiquitin ligase RNF183.2018
Author(s)
Wu Y, Guo XP, Kanemoto S, Maeoka Y, Saito A, Asada R, Matsuhisa K, Ohtake Y, Imaizumi K, Kaneko M.
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Journal Title
PLoS One
Volume: 13
Issue: 1
Pages: e0190407-e0190407
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Suppression of transcription factor OASIS ameliorated kidney fibrosis2019
Author(s)
Masanori Obana, Ayaha Yamamoto, Takafumi Nakae, Yoshiaki Miyake, Takeo Harada, Sayuri Mitsuoka, Shunsuke Noda, Makiko Maeda, Kazunori Imaizumi, Kotaro Matsumoto, Yasushi Fujio.
Organizer
The American Society of Nephrology
Related Report
Int'l Joint Research
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